CD22: A Regulator of Innate and Adaptive B Cell Responses and Autoimmunity

Clark, Edward A.; Giltiay, Natalia V.

doi:10.3389/fimmu.2018.02235

Cited by 197T-cell and B-cell ImmunologyGlycosylation and Glycoproteins ResearchSystemic Lupus Erythematosus Research

CD22: A Regulator of Innate and Adaptive B Cell Responses and Autoimmunity

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Clark, Edward A., Giltiay, Natalia V.·2018·Frontiers in Immunology

DOI 10.3389/fimmu.2018.02235PMC PMC6173129

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Abstract

CD22 (Siglec 2) is a receptor predominantly restricted to B cells. It was initially characterized over 30 years ago and named "CD22" in 1984 at the 2nd International workshop in Boston (1). Several excellent reviews have detailed CD22 functions, CD22-regulated signaling pathways and B cell subsets regulated by CD22 or Siglec G (2-4). This review is an attempt to highlight recent and possibly forgotten findings. We also describe the role of CD22 in autoimmunity and the great potential for CD22-based immunotherapeutics for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE).

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SYK is the central kinase that instructs signaling and effector functions downstream of TREM2, CD33, and CD22 receptors.
“In addition, SYK has been identified as the central kinase that instructs signaling and effector functions downstream of TREM2, CD33, and CD22 receptors (Clark and Giltiay, 2018; Wissfeld et al., 2021; Yao et al., 2019).”
From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Clark and Giltiay, 2018
The Introduction and “Regulation of bcr signaling by CD22” describe CD22-mediated signaling, so the paper supports the CD22 signaling context. But those sections describe Lyn, SHP-1 and other signaling partners; they do not identify SYK as a central kinase downstream of CD22. The other receptors appear alongside additional citations, so this verdict is limited to what Clark and Giltiay support. (LLM, conf=0.83)
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“in a different approach used in situ photoaffnity crosslinking of glycan ligands to CD22 (28).”
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“Mice expressing all of CD22 except the extracellular domains 1 and 2 (CD2211-2 mice) have reduced MZ B cells but normal TI-2 Ab responses (15, 36, 37), so a MZ B cell deficiency alone is not sufficient to lead to impaired TI2 Ab responses.”
Background
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Background
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Background
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Background
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Background
IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Igα/β
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Background
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“The fact that deletion of Cd22 alone might not be sufficient to drive autoimmune disease in some mice can be explained by some functional redundancy between CD22 and SiglecG, another Siglec family member, expressed on B cells also implicated in the regulation of BCR signaling (2, 76, 77).”
Background
CD22 Regulates B Cell Receptor-mediated Signals via Two Domains That Independently Recruit Grb2 and SHP-1*
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Self-citation
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BackgroundSelf-citation
TLR‐mediated STAT3 and ERK activation controls IL‐10 secretion by human B cells
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“Thus, targeting CD22 may restore IL-10 production by regulatory B cells, reported to be impaired in SLE patients (126).”
BackgroundInfluential
The role of CD22 and Siglec-G in B-cell tolerance and autoimmune disease
Müller, J., & Nitschke, L. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.54 · Cited by 120 · cited 1× · see citing works
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Background
Decrease of sialic acid residues as aneat-mesignal on the surface of apoptotic lymphocytes
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Background
Identification of CD22 Ligands on Bone Marrow Sinusoidal Endothelium Implicated in CD22-dependent Homing of Recirculating B Cells
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“The endothelial cells in BM sinusoids express the α2,6-linked sialic acid ligand for CD22 (59).”
Background
Overexpression of TLR7 promotes cell-intrinsic expansion and autoantibody production by transitional T1 B cells
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“Similar egress of MZ B cells can be found in other autoimmune models, particularly those associated with TLR7 overexpression (78, 79).”
BackgroundSelf-citation
CD22 Is a Recycling Receptor That Can Shuttle Cargo between the Cell Surface and Endosomal Compartments of B Cells
O’Reilly, M. K., Tian, H., & Paulson, J. C. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1003005 · Cited by 116 · cited 1× · see citing works
“CD22 is an endocytic receptor that recycles between the cell surface and the endosomes, where endosomal TLRs resides (41).”
Background
Siglecs as sensors of self in innate and adaptive immune responses
Paulson, J. C., Macauley, M. S., & Kawasaki, N. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06362.x · Cited by 113 · cited 2× · see citing works
“Siglec-G/10 has been shown to suppress TLR4 signaling and NFkB activation by forming a complex with CD24, which binds endogenous TLR ligands such as HSP and HMGB1, but not LPS, providing selective repression of the inflammatory responses to Danger-Associated Molecular Patterns (DAMPs), but not pathogen-associated mole…”
Background
CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity
Chen, J., Mclean, P., Neel, B., Okunade, G. W., Shull, G., & Wortis, H. (2004) · Nature Immunology · doi:10.1038/ni1072 · Cited by 104 · cited 2× · see citing works
“(25) found that CD22 can associate with plasma membrane calcium ATPase (PMCA) to enhance calcium efflux after BCR ligation; this association only occurs if CD22 is tyrosine phosphorylated.”
Background
Stimulation by phospholipids of a protein-tyrosine-phosphatase containing two src homology 2 domains.
Zhao, Z.-Z., Shen, S.-H., & Fischer, E. H. (1993) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.90.9.4251 · Cited by 103 · cited 1×
“1C) to the plasma membrane may increase its enzymatic activity more than a 1,000 fold (17).”
Background
Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies
Leonard, J. P., & Goldenberg, D. (2007) · Oncogene · doi:10.1038/sj.onc.1210370 · Cited by 101 · cited 4×
“The first fullyhumanized anti-CD22 IgG1 antibody, Epratuzumab (Emab) has been evaluated in clinical trials of B-cell NHL and ALL (113).”
BackgroundInfluential
Nanoscale organization and dynamics of the siglec CD22 cooperate with the cytoskeleton in restraining BCR signalling
Gasparrini, F., Feest, C., Bruckbauer, A., Mattila, P. K., Müller, J., Nitschke, L., Bray, D., & Batista, F. D. (2015) · EMBO Journal · doi:10.15252/embj.201593027 · Cited by 95 · cited 2× · see citing works
“(29) used super-resolution microscopy to examine the interactions of CD22 with the actin cytoskeleton.”
Background
Ig domains 1 and 2 of murine CD22 constitute the ligand-binding domain and bind multiple sialylated ligands expressed on B and T cells.
Law, C.-L., Aruffo, A., Chandran, K. A., Doty, R., & Clark, E. A. (1995) · Journal of Immunology · doi:10.4049/jimmunol.155.7.3368 · Cited by 95 · cited 3× · see citing works
“Ligands for CD22 have been identified on CD22 itself and on T cells (28, 30, 43).”
BackgroundSelf-citation
CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade.
Tuscano, J., Riva, A., Toscano, S. N., Tedder, T. F., & Kehrl, J. (1999) · Blood · doi:10.1182/blood.v94.4.1382.416k14_1382_1392 · Cited by 91
Engagement of the adhesion receptor CD22 triggers a potent stimulatory signal for B cells and blocking CD22/CD22L interactions impairs T-cell proliferation.
Tuscano, J., Engel, P., Tedder, T. F., & Kehrl, J. (1996) · Blood · doi:10.1182/blood.v87.11.4723.bloodjournal87114723 · Cited by 91 · cited 1×
“Thus, CD22may engage CD22 ligands in trans on T cells and affect T cell activation (14, 44).”
Background
Cd22a PRE-mRNA Dysregulated Expression of the Cd22 Gene as a Result of a Short Interspersed Nucleotide Element Insertion in Cd22a Lupus-Prone Mice1
Mary, C., Laporte, C., Parzy, D., Santiago, M.-L., Stefani, F., Lajaunias, F., Parkhouse, R., O'Keefe, T. L., Neuberger, M., Izui, S., et al. (2000) · Journal of Immunology · doi:10.4049/jimmunol.165.6.2987 · Cited by 82 · see citing works
B-cell selection and the development of autoantibodies
Giltiay, N. V., Chappell, C. P., & Clark, E. A. (2012) · Arthritis Research & Therapy · doi:10.1186/ar3918 · Cited by 80 · cited 1× · see citing works
“We found that in healthy conditions newly-formed transitional (TR) B cells in both human and mice express relatively high levels of CD22 (Giltiay NV, unpublished data), which might function to prevent unwanted activation, as a number of studies have shown that TR B cells express BCRs that are polyreactive and can bind…”
BackgroundSelf-citation
Rheumatoid arthritis patients display B-cell dysregulation already in the naïve repertoire consistent with defects in B-cell tolerance
Wang, Y., Lloyd, K. A., Melas, I. N., Zhou, D., Thyagarajan, R., Lindqvist, J., Hansson, M., Svärd, A., Mathsson‐Alm, L., Kastbom, A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-56279-0 · Cited by 80 · see citing works
Targeting CD22 in B-cell Malignancies: Current Status and Clinical Outlook
Sullivan-Chang, L., O'Donnell, R., & Tuscano, J. (2013) · BioDrugs · doi:10.1007/s40259-013-0016-7 · Cited by 79
Human B-lymphocytes Express α2-6-Sialylated 6-Sulfo-N-acetyllactosamine Serving as a Preferred Ligand for CD22/Siglec-2*
Kimura, N., Ohmori, K., Miyazaki, K., Izawa, M., Matsuzaki, Y., Yasuda, Y., Takematsu, H., Kozutsumi, Y., Moriyama, A., & Kannagi, R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702341200 · Cited by 74 · see citing works
Regulation of B cell development and B cell signalling by CD22 and its ligands alpha2,6-linked sialic acids.
Ghosh, S., Bandulet, C., & Nitschke, L. (2006) · International Immunology · doi:10.1093/intimm/dxh402 · Cited by 74
SHP1 and SHP2 protein-tyrosine phosphatases associate with betac after interleukin-3-induced receptor tyrosine phosphorylation. Identification of potential binding sites and substrates.
Bone, H., Dechert, U., Jirik, F. R., Schrader, J. W., & Welham, M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.22.14470 · Cited by 72 · see citing works
CD22, a B cell-specific receptor, mediates adhesion and signal transduction.
Clark, E. A. (1993) · Journal of Immunology · doi:10.4049/jimmunol.150.11.4715 · Cited by 71 · cited 1×
“CD22 has long been known to be an adhesion molecule (1).”
BackgroundSelf-citation
Analysis of Tyrosine Phosphorylation-dependent Interactions between Stimulatory Effector Proteins and the B Cell Co-receptor CD22*
Yohannan, J., Wienands, J., Coggeshall, K., & Justement, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.26.18769 · Cited by 70 · cited 3× · see citing works
“is a non-conservative amino acid substitution (G745D) within the cytoplasmic domain, proximal to a YXXM motif that is a binding site for PI3K (7).”
BackgroundInfluential
Beyond apoptosis in lupus
Colonna, L., Lood, C., & Elkon, K. B. (2014) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000083 · Cited by 69 · cited 1× · see citing works
“This might occur in SLE where the accumulation of necrotic/apoptotic cells and improper clearance play a major role in promoting immune cell activation (109).”
Background
Subcellular localization of Grb2 by the adaptor protein Dok‐3 restricts the intensity of Ca2+ signaling in B cells
Stork, B., Neumann, K., Goldbeck, I., Alers, S., Kähne, T., Naumann, M., Engelke, M., & Wienands, J. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601557 · Cited by 69 · cited 1× · see citing works
“Grb2 has been previously implicated in the negative regulation of Ca2+ in B cells through its localization by the adaptor protein Dok-3 to the plasma membrane and subsequent inhibition of Btk (27).”
Background
Unmasking of CD22 Co-receptor on Germinal Center B-cells Occurs by Alternative Mechanisms in Mouse and Man
Macauley, M. S., Kawasaki, N., Peng, W., Wang, S.-H., He, Y., Arlian, B. M., McBride, R., Kannagi, R., Khoo, K., & Paulson, J. C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.691337 · Cited by 69 · cited 2× · see citing works
“This model fits well with a study that showed changes in the glycosylation patterns due to altered enzyme activity in the GC, leading to unmasking of CD22 on GC B cells compared naive and memory B-cells, (54).”
BackgroundResult
The mechanistic impact of CD22 engagement with epratuzumab on B cell function: Implications for the treatment of systemic lupus erythematosus.
Dörner, T., Shock, A., Goldenberg, D., & Lipsky, P. (2015) · Autoimmunity Reviews · doi:10.1016/j.autrev.2015.07.013 · Cited by 67 · see citing works
REFINEMENT OF THE CLINICAL PHENOTYPE IN MUSK-RELATED CONGENITAL MYASTHENIC SYNDROMES
Mihaylova, V., Salih, M. A., Mukhtar, M., Abuzeid, H., El-Sadig, S., von der Hagen, M., Huebner, A., Nürnberg, G., Abicht, A., Müller, J., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c3fce9 · Cited by 67 · cited 1× · see citing works
“This triple chimera targeted selectively autoreactive B cells and the simultaneous engagement of the BCR, CD22 and, FcgRIIb inhibited antiDNA Ab production and delayed the development of disease (130).”
Background
CD22 Regulates Adaptive and Innate Immune Responses of B Cells
Kawasaki, N., Rademacher, C., & Paulson, J. (2010) · Journal of Innate Immunity · doi:10.1159/000322375 · Cited by 66 · cited 4× · see citing works
“Kawasaki et al. concluded that this hyperresponsiveness to TLR agonists was not due to CD22−/− B cells expressing higher levels of TLRs; rather their results suggest that CD22 may normally function during TLR signaling of B cells to activate suppressors of cytokine signaling (SOCS) SOCS1 and SOCS3 proteins that are kn…”
BackgroundInfluential
The shared tumor-specific antigen encoded by mouse geneP1A is a target not only for cytolytic T lymphocytes but also for tumor rejection
Brändle, D., Bilsborough, J., Rülicke, T., Uyttenhove, C., Boon, T., & den Eynde, B. J. V. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199812)28:12 · Cited by 62 · see citing works
Identification of the gene variations in human CD22
Hatta, Y., Tsuchiya, N., Matsushita, M., Shiota, M., Hagiwara, K., & Tokunaga, K. (1999) · Immunogenetics · doi:10.1007/s002510050494 · Cited by 62 · cited 3× · see citing works
“(81) performed a systematic variation screening of the humanCD22 gene and studied possible associations between CD22 polymorphisms and susceptibility to RA and SLE.”
Background
Dendritic Cell-Dependent Inhibition of B Cell Proliferation Requires CD221
Santos, L., Draves, K. E., Boton, M., Grewal, P., Marth, J., & Clark, E. (2008) · Journal of Immunology · doi:10.4049/jimmunol.180.7.4561 · Cited by 59 · cited 13×
“Surprisingly, ST6Gal1−/− DCs were just as efficient as wildtype DCs in inhibiting B cell responses to either BCR-ligation or LPS (35, 61), suggesting that CD22 may mediate inhibition of B cells through an interaction not dependent on ST6Gal1.”
BackgroundInfluentialSelf-citation
CD22 expression on blastic plasmacytoid dendritic cell neoplasms and reactivity of anti‐CD22 antibodies to peripheral blood dendritic cells
Reineks, E. Z., Osei, E., Rosenberg, A., Auletta, J., & Meyerson, H. (2009) · Cytometry. Part B, Clinical cytometry · doi:10.1002/cyto.b.20469 · Cited by 58 · cited 1× · see citing works
“CD22 has also been reported to be expressed on human plasmacytoid DC tumors and follicular dendritic cells (63, 64).”
Background
Efficacy of Epratuzumab, an Anti‐CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythematosus Patients With Associated Sjögren's Syndrome
Gottenberg, J., Dörner, T., Bootsma, H., Devauchelle-Pensec, V., Bowman, S., Mariette, X., Bartz, H., Oortgiesen, M., Shock, A., Koetse, W., et al. (2018) · Arthritis & Rheumatology · doi:10.1002/art.40425 · Cited by 54 · see citing works
The B Cell Coreceptor CD22 Associates with AP50, a Clathrin-Coated Pit Adapter Protein, Via Tyrosine-Dependent Interaction1
John, B., Herrin, B., Raman, C., Wang, Y.-N., Bobbitt, K., Brody, B., & Justement, L. (2003) · Journal of Immunology · doi:10.4049/jimmunol.170.7.3534 · Cited by 53 · see citing works
Organization of the murine Cd22 locus. Mapping to chromosome 7 and characterization of two alleles.
Law, C.-L., Torres, R. M., Sundberg, H., Parkhouse, R., Brannan, C., Copeland, N., Jenkins, N., & Clark, E. A. (1993) · Journal of Immunology · doi:10.4049/jimmunol.151.1.175 · Cited by 51 · cited 2× · see citing works
“This brings us back to the original isolation of genomic clones of mouse Cd22 which demonstrated the presence of at least two (or more) Cd22 alleles (71).”
BackgroundSelf-citation
Esterases and autoimmunity: the Sialic acid acetylesterase pathway and the regulation of peripheral B cell tolerance
Pillai, S., Cariappa, A., & Pirnie, S. P. (2009) · Trends in immunology · doi:10.1016/j.it.2009.07.006 · Cited by 49 · see citing works
CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous toll-like receptor 7 ligand Sm/RNP
Akatsu, C., Shinagawa, K., Numoto, N., Liu, Z., Ucar, A. K., Aslam, M., Phoon, S., Adachi, T., Furukawa, K., Ito, N., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160560 · Cited by 49 · cited 1× · see citing works
“A recent study showed that CD72 binds to endogenous TLR7 ligand Sm/RNP and inhibits TLR7-driven B cell responses (110).”
Background
Epratuzumab inhibits the production of the proinflammatory cytokines IL-6 and TNF-α, but not the regulatory cytokine IL-10, by B cells from healthy donors and SLE patients
Fleischer, V., Sieber, J., Fleischer, S. J., Shock, A., Heine, G., Daridon, C., & Dörner, T. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0686-2 · Cited by 47
Epratuzumab for the treatment of systemic lupus erythematosus
Geh, D., & Gordon, C. (2018) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2018.1450141 · Cited by 47 · cited 2× · see citing works
“The safety and efficacy of Emab in SLE have been evaluated in several clinical trials (120).”
Background
Immune Complex-Mediated Enhancement of Secondary Antibody Responses
Goins, C. L., Chappell, C. P., Shashidharamurthy, R., Selvaraj, P., & Jacob, J. (2010) · Journal of Immunology · doi:10.4049/jimmunol.0902530 · Cited by 46 · cited 1×
“Thus, both CGG-specific Tfh cells and CGG-anti-CGG immune complexes that can be taken up by FcγR cells may have contributed to the rapid hyperproliferative and extrafollicular B cell responses observed, as has been reported (50).”
Result
Differentially Regulated Expression and Function of CD22 in Activated B-1 and B-2 Lymphocytes1
Lajaunias, F., Nitschke, L., Moll, T., Martínez-Soria, E., Semac, I., Chicheportiche, Y., Parkhouse, R., & Izui, S. (2002) · Journal of Immunology · doi:10.4049/jimmunol.168.12.6078 · Cited by 46 · cited 5×
“In contrast, BCR crosslinking of CD5+ B1 B cells did not change the expression levels of CD22, and B1 cells downregulated CD22 in response to LPS or CpG (88).”
BackgroundInfluential
Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22
Chen, W., Sigal, D., Saven, A., & Paulson, J. (2011) · Leukemia and Lymphoma · doi:10.3109/10428194.2011.604755 · Cited by 44 · cited 1×
“Other approaches for targeting CD22 in B cell malignancies have utilized high-affinity CD22 ligands (117, 118).”
Background
B cell defects in SLP65/BLNK‐deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling
Gerlach, J., Ghosh, S., Jumaa, H., Reth, M., Wienands, J., Chan, A., & Nitschke, L. (2003) · European Journal of Immunology · doi:10.1002/eji.200324290 · Cited by 43 · cited 1× · see citing works
“SLP-76 and BLNK may also be SHP-1 substrates in B cells (23, 24).”
Background
Transitional and marginal zone B cells have a high proportion of unmasked CD22: implications for BCR signaling.
Danzer, C.-P., Collins, B. E., Blixt, O., Paulson, J., & Nitschke, L. (2003) · International Immunology · doi:10.1093/intimm/dxg114 · Cited by 43
Molecular interactions of SHP1 and SHP2 in IL-3-signalling.
Wheadon, H., Paling, N. R. D., & Welham, M. (2002) · Cellular Signalling · doi:10.1016/s0898-6568(01)00241-8 · Cited by 39 · cited 1× · see citing works
“Yes, phosphorylated ITIMs can be dephosphorylated by SHP-1 in vitro (18, 19), but in vitro data do not necessarily reflect in vivo substrates.”
Background
Association of CD22 gene polymorphism with susceptibility to limited cutaneous systemic sclerosis.
Yuki, H., Tsuchiya, N., Hasegawa, M., Fujimoto, M., Takehara, K., Tokunaga, K., & Sato, S. (2007) · Tissue Antigens · doi:10.1111/j.1399-0039.2007.00801.x · Cited by 38 · cited 2× · see citing works
“2304C > A (P768P, rs34826052) located within exon 13 of the CD22 gene (86).”
Background
Associations of genetic polymorphisms of Siglecs with human diseases
Angata, T. (2014) · Glycobiology · doi:10.1093/glycob/cwu043 · Cited by 38 · cited 1× · see citing works
“Genetic variants of CD22, or enzymes involved in the glycosylation of ligands of CD22 have been linked to susceptibility in human autoimmune diseases (80, 81).”
Background
Siglec-G Deficiency Leads to More Severe Collagen-Induced Arthritis and Earlier Onset of Lupus-like Symptoms in MRL /lpr Mice
Bökers, S., Urbat, A., Daniel, C., Amann, K., Smith, K. G. C., Espéli, M., & Nitschke, L. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1303367 · Cited by 37 · cited 1× · see citing works
“The fact that deletion of Cd22 alone might not be sufficient to drive autoimmune disease in some mice can be explained by some functional redundancy between CD22 and SiglecG, another Siglec family member, expressed on B cells also implicated in the regulation of BCR signaling (2, 76, 77).”
Background
Severely Impaired B Lymphocyte Proliferation, Survival, and Induction of the c-Myc:Cullin 1 Ubiquitin Ligase Pathway Resulting from CD22 Deficiency on the C57BL/6 Genetic Background 1
Poe, J., Haas, K. M., Uchida, J., Lee, Y., Fujimoto, M., & Tedder, T. (2004) · Journal of Immunology · doi:10.4049/jimmunol.172.4.2100 · Cited by 36 · cited 2×
“B cell proliferation induced via the “T cell-help” CD40 receptor is elevated in CD22 B cells (37).”
Background
Human CD22 Inhibits Murine B-cell Receptor Activation in a Human CD22 Transgenic Mouse Model
Bednar, K. J., Shanina, E., Ballet, R., Connors, E., Duan, S.-T., Juan, J., Arlian, B. M., Kulis, M., Butcher, E., Fung-Leung, W., et al. (2017) · Journal of Immunology · doi:10.4049/jimmunol.1700898 · Cited by 33 · cited 1× · see citing works
“This new model may provide a valuable tool to study the function of human CD22 in vivo and for future preclinical studies (132).”
Method
CD22-Binding Synthetic Sialosides Regulate B Lymphocyte Proliferation Through CD22 Ligand-Dependent and Independent Pathways, and Enhance Antibody Production in Mice
Matsubara, N., Imamura, A., Yonemizu, T., Akatsu, C., Yang, H., Ueki, A., Watanabe, N., Abdu-Allah, H., Numoto, N., Takematsu, H., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00820 · Cited by 32 · cited 4× · see citing works
“The natural ligands for CD22 apparently do not play a direct role in regulating proliferative responses to TLR agonists since CD22 ligand-deficient ST6Gal1−/− B cells have normal responses to LPS and CpG (40).”
BackgroundInfluential
Targeting CD22 with the monoclonal antibody epratuzumab modulates human B-cell maturation and cytokine production in response to Toll-like receptor 7 (TLR7) and B-cell receptor (BCR) signaling
Giltiay, N., Shu, G., Shock, A., & Clark, E. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1284-2 · Cited by 32 · cited 8× · see citing works
“Emab inhibits the activation and the expression of PRDM1/Blimp1 in response to BCR and TLR7 stimulation in a subset of CD27−IgD− double-negative (DN)memory B-cells (104), known to be elevated in SLE patients with more active disease (127).”
BackgroundInfluentialSelf-citation
Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool
Li, Y.-F., Xu, S.-L., Ou, X.-J., & Lam, K.-P. (2014) · Nature Communications · doi:10.1038/ncomms5273 · Cited by 32 · cited 1×
“SHP-1, which can be recruited to bind CD22, plays a role in GC maintenance and memory cell development (51, 52).”
Background
An extracatalytic function of CD45 in B cells is mediated by CD22
Coughlin, S. E., Noviski, M., Mueller, J., Chuwonpad, A., Raschke, W., Weiss, A., & Zikherman, J. (2015) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1519925112 · Cited by 30 · cited 1×
“(32) also implicated extracellular CD45 in the regulation of CD22.”
Background
SLP‐76 is recruited to CD22 and dephosphorylated by SHP‐1, thereby regulating B cell receptor‐induced c‐Jun N‐terminal kinase activation
Mizuno, K., Tagawa, Y., Watanabe, N., Ogimoto, M., & Yakura, H. (2005) · European Journal of Immunology · doi:10.1002/eji.200425465 · Cited by 27 · cited 1× · see citing works
“SLP-76 and BLNK may also be SHP-1 substrates in B cells (23, 24).”
Background
Cd72c Is a Modifier Gene that Regulates Faslpr-Induced Autoimmune Disease
Xu, M., Hou, R., Sato-Hayashizaki, A., Man, R., Zhu, C., Wakabayashi, C., Hirose, S., Adachi, T., & Tsubata, T. (2013) · Journal of Immunology · doi:10.4049/jimmunol.1203576 · Cited by 27 · see citing works
CD22 Is Required for Protection against West Nile Virus Infection
Ma, D. Y., Suthar, M., Kasahara, S., Gale, M., & Clark, E. (2013) · Journal of Virology · doi:10.1128/jvi.02368-12 · Cited by 27 · cited 4×
“CD22 mice are highly susceptible to infection by West Nile virus (WNV) and die within 10 days post-infection (57).”
BackgroundInfluentialSelf-citation
Autoantibody‐mediated regulation of B cell responses by functional anti‐CD22 autoantibodies in patients with systemic sclerosis
Odaka, M., Hasegawa, M., Hamaguchi, Y., Ishiura, N., Kumada, S., Matsushita, T., Komura, K., Sato, S., Takehara, K., & Fujimoto, M. (2010) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2009.04059.x · Cited by 27 · cited 1×
“Interestingly, antiCD22 Abs capable of inhibiting tyrosine phosphorylation of CD22 have been found in both SSc and SLE patients, which might be another, yet-to-be-explored, mechanism for regulation of CD22 function (93).”
Background
Targeted Approaches to Inhibit Sialylation of Multiple Myeloma in the Bone Marrow Microenvironment
Natoni, A., Bohara, R., Pandit, A., & O'Dwyer, M. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00252 · Cited by 25 · see citing works
CD22 Regulates Time Course of Both B Cell Division and Antibody Response1
Onodera, T., Poe, J., Tedder, T., & Tsubata, T. (2008) · Journal of Immunology · doi:10.4049/jimmunol.180.2.907 · Cited by 25 · cited 1× · see citing works
“(49) reported that after immunization CD22 B cells, including GC B cells, rapidly expand and generate short-lived AFCs and antibodies.”
Background
M89V Sialic Acid Acetyl Esterase (SIAE) and All Other Non-Synonymous Common Variants of This Gene Are Catalytically Normal
Chellappa, V., Taylor, K. N., Pedrick, K., Donado, C., Netravali, I., Haider, K., Cariappa, A., Dalomba, N. F., & Pillai, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053453 · Cited by 23 · see citing works
Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules.
Fehr, T., López-Macías, C., Odermatt, B., Torres, R. M., Schubart, D. B., O'Keefe, T. L., Matthias, P., Hengartner, H., & Zinkernagel, R. (2000) · International Immunology · doi:10.1093/intimm/12.9.1275 · Cited by 23 · cited 1× · see citing works
“For example, CD22 mice infected with lymphocytic choriomeningitis virus, vesicular stomatitis virus (65), or Staphylococcus aureus (66) have no differences in survival compared to wild-type (WT) mice.”
Background
Follicular dendritic cells adhere to fibronectin and laminin fibers via their respective receptors.
Ogata, T., Yamakawa, M., Imai, Y., & Takahashi, T. (1996) · Blood · doi:10.1182/blood.v88.8.2995.bloodjournal8882995 · Cited by 23 · cited 1×
“CD22 has also been reported to be expressed on human plasmacytoid DC tumors and follicular dendritic cells (63, 64).”
Background
Differential control of CD22 ligand expression on B and T lymphocytes, and enhanced expression in murine systemic lupus.
Lajaunias, F., Ida, A., Kikuchi, S., Fossati-Jimack, L., Martínez-Soria, E., Moll, T., Law, C., & Izui, S. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11021 · Cited by 22 · cited 1×
“Cognate interactions between B and T cells are critical for GC initiation and maintenance, and CD22 ligands (CD22Ls) are expressed on T cells as well as B cells (30, 53).”
Background
CD22 is required for formation of memory B cell precursors within germinal centers
Chappell, C. P., Draves, K. E., & Clark, E. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174661 · Cited by 20 · cited 3×
“Unlike SHP-1 deletion, however, GCs are not completely ablated in the absence of CD22; rather, a small subset of CXCR4CD38 PNA GC B cells fail to develop that normally appear early in the immune response (48).”
BackgroundInfluentialSelf-citation
Engagement of CD22 on B cells with the monoclonal antibody epratuzumab stimulates the phosphorylation of upstream inhibitory signals of the B cell receptor
Lumb, S., Fleischer, S. J., Wiedemann, A., Daridon, C., Maloney, A., Shock, A., & Dörner, T. (2016) · Journal of cell communication and signaling · doi:10.1007/s12079-016-0322-1 · Cited by 20 · cited 6×
“Grb2 has been previously implicated in the negative regulation of Ca2+ in B cells through its localization by the adaptor protein Dok-3 to the plasma membrane and subsequent inhibition of Btk (27).”
BackgroundInfluential
Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding.
Nitschke, L., Lajaunias, F., Moll, T., Ho, L.-Z., Martínez-Soria, E., Kikuchi, S., Santiago‐Raber, M., Dix, C., Parkhouse, R., & Izui, S. (2006) · International Immunology · doi:10.1093/intimm/dxh349 · Cited by 20 · cited 3×
“(72) showed that CD22 encoded by the Cd22a allele expressed on B cells in lupus-prone mice is less efficient in binding to CD22L as compared to the Cd22b counterparts.”
BackgroundResultInfluential
Autoregulatory function of interleukin-10-producing pre-naïve B cells is defective in systemic lupus erythematosus
Sim, J., Kim, H.-R., Chang, S., Kim, I., Lipsky, P., & Lee, J. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0687-1 · Cited by 19 · cited 1×
“Thus, targeting CD22 may restore IL-10 production by regulatory B cells, reported to be impaired in SLE patients (126).”
Background
Myosin is an in vivo substrate of the protein tyrosine phosphatase (SHP-1) after mIgM cross-linking.
Baba, T., Fusaki, N., Shinya, N., Iwamatsu, A., & Hozumi, N. (2003) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/s0006-291x(03)00542-4 · Cited by 19 · cited 1× · see citing works
“Using a catalytically inactive trapping mutant of SHP-1, the Hozumi group showed that after BCR ligation both myosin and CD72 are substrates for SHP-1 (21, 22).”
CD22 Promotes B-1b Cell Responses to T Cell–Independent Type 2 Antigens
Haas, K. M., Johnson, K. L., Phipps, J. P., & Do, C. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701578 · Cited by 16 · cited 3× · see citing works
“found that CD22 mice have reduced primary Ab responses to NP-OVA in alum (36, 38).”
Background
Bone marrow dendritic cell mediated regulation of TLR and BCR signaling in B cells
Sindhava, V., Tuna, H., Gachuki, B. W., DiLillo, D., Avdiushko, M. G., Onami, T. M., Tedder, T., Cohen, D., & Bondada, S. (2012) · Journal of Immunology · doi:10.4049/jimmunol.1101352 · Cited by 16 · cited 11×
“Surprisingly, ST6Gal1−/− DCs were just as efficient as wildtype DCs in inhibiting B cell responses to either BCR-ligation or LPS (35, 61), suggesting that CD22 may mediate inhibition of B cells through an interaction not dependent on ST6Gal1.”
BackgroundInfluential
Epratuzumab for Systemic Lupus Erythematosus*
Wallace, D. J., & Goldenberg, D. (2013) · Lupus · doi:10.1177/0961203312469692 · Cited by 15 · cited 2×
“There has been a significant interest in adopting CD22targeted agents, such as Emab as therapies for autoimmune diseases, and in particular, for SLE (120, 121).”
Background
Decreased CD22 expression and intracellular signaling aberrations in B cells of patients with systemic sclerosis
Melissaropoulos, K., & Liossis, S. (2018) · Rheumatology International · doi:10.1007/s00296-018-4076-3 · Cited by 14 · cited 1× · see citing works
“SSc patients may also have decreases in CD22 expression and reduced CD22 phosphorylation (92).”
Background
The role of B cell CD22 expression in Staphylococcus aureus arthritis and sepsis.
Gjertsson, I., Nitschke, L., & Tarkowski, A. (2004) · Microbes and infection · doi:10.1016/j.micinf.2003.12.013 · Cited by 14 · cited 1× · see citing works
“For example, CD22 mice infected with lymphocytic choriomeningitis virus, vesicular stomatitis virus (65), or Staphylococcus aureus (66) have no differences in survival compared to wild-type (WT) mice.”
Background
CD19 Signaling Pathways Play a Major Role for Murine AIDS Induction and Progression
Knoetig, S., Torrey, T., Naghashfar, Z., McCarty, T., & Morse, H. (2002) · Journal of Immunology · doi:10.4049/jimmunol.169.10.5607 · Cited by 14 · cited 1×
“CD22-deficiency not only leads to increased susceptibility toWNV (55), but also accelerates murine AIDS MAIDS induced by a murine leukemia virus (67), CD22 mice had a more rapid onset of splenomegaly and lymphadenopathy 4 weeks after infection.”
Background
Besides an ITIM/SHP-1-dependent pathway, CD22 collaborates with Grb2 and plasma membrane calcium-ATPase in an ITIM/SHP-1-independent pathway of attenuation of Ca2+i signal in B cells
Chen, J., Wang, H., Xu, W.-P., Wei, S.-S., Li, H., Mei, Y., Li, Y.-G., & Wang, Y.-P. (2016) · OncoTarget · doi:10.18632/oncotarget.9794 · Cited by 13 · cited 2× · see citing works
“(25, 26) propose that PMCA regulates Ca2+ in B cells through its interaction with CD22 via a SHP-1-independent pathway.”
Background
Peripheral B cell receptor editing may promote the production of high‐affinity autoantibodies in CD22‐deficient mice
Yarkoni, Y., Fischel, R., Kat, I., Yachimovich‐Cohen, N., & Eilat, D. (2006) · European Journal of Immunology · doi:10.1002/eji.200636190 · Cited by 12
CD19/22 balance relates to improvement of disease activity in systemic lupus erythematosus
Suzuki, J., Nakano, S., Nakairi, Y., Mitsuo, A., Amano, H., Morimoto, S., Tokano, Y., & Takasaki, Y. (2006) · Modern Rheumatology · doi:10.3109/s10165-006-0497-z · Cited by 7 · cited 1×
“Relatively few studies have examined the expression of CD22 on B cells from SLE patients; one study reported a decrease in CD22 levels on B cells from SLE patients with active disease; another study showed an association between disease improvement and increased CD22 expression after treatment (90, 91).”
Background
STALing B cell responses with CD22.
Chappell, C. P., & Clark, E. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69670 · Cited by 4 · cited 1×
“The administration of these SIGLEC-engaging Ag-liposomes (STALs) in mice decreased Ab responses upon a second challenge with the same particles without CD22L, suggesting the induction of Ag-specific immunogenic tolerance (128, 129).”
BackgroundSelf-citation

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9 of the 138 references couldn’t be matched to a known paper.

Research works printed but not linked: 9

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CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response
Wu, Z., Zhou, J., Xiao, Y., Ming, J., Zhou, J., Dong, F., Zhou, X., Xu, Z., Zhao, X., Lei, P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.865596 · Cited by 63 · see citing works
“In contrast, CD22 (Siglec 2) is a regulatory receptor predominantly restricted to B cells, which inhibits both BCR and TLR signaling through four ITIMs (41).”
Background
Antibody–drug conjugates in cancer therapy: mechanisms and clinical studies
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Sialic Acid-Siglec Axis in Human Immune Regulation, Involvement in Autoimmunity and Cancer and Potential Therapeutic Treatments
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Pregnancy enables antibody protection against intracellular infection
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“Future studies will have to also survey the contribution of other immune cell types to the development of PTOA since genes associated with B-cell activation, such as Blk,(64) Blnk, (65) Cd22,(66) Cd79a,(67) and Cd79b,(68) were downregulated in the injured joints tread with LPS in both male and female cohorts.”
Background
Roles for Siglec-glycan interactions in regulating immune cells
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CD22 blockade modulates microglia activity to suppress neuroinflammation following intracerebral hemorrhage
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Profiling the Atlantic Salmon IgM+ B Cell Surface Proteome: Novel Information on Teleost Fish B Cell Protein Repertoire and Identification of Potential B Cell Markers
Peñaranda, M., Jensen, I., Tollersrud, L. G., Bruun, J., & Jørgensen, J. B. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00037 · Cited by 34 · see citing works
CD22 Blockage Restores Age-Related Impairments of Microglia Surveillance Capacity
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Upregulation of CD22 by Chidamide promotes CAR T cells functionality
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“It consists of seven extracellular IgG-like domains and a 141-amino acid-long cytoplasmic tail [32, 33] (Fig.”
Background
Impact of Siglecs on autoimmune diseases
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“It has been shown that CD22 coordinates its inhibitory regulation 126 of B cells by cooperating with calcium pumps and reducing the stores of Ca 2+ , turning the PMCAs into a transient regulator of lymphocyte activation.”
Background
Oral obeldesivir provides postexposure protection against Marburg virus in nonhuman primates
Cross, R., Woolsey, C. B., Prasad, A., Borisevich, V., Agans, K., Deer, D., Harrison, M. B., Dobias, N. S., Fenton, K. A., Cihlář, T., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03496-y · Cited by 27 · see citing works
“Notably, BTLA and CD22 are genes whose protein products are key regulators of B cell activity 27,28 , helping to prevent excessive immune responses and autoimmunity.”
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“Variations and polymorphisms in the CD22 gene have been correlated with an increased susceptibility to autoimmune conditions, such as SLE [175].”
The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2–associated multisystem inflammatory syndrome in children
Benamar, M., Chen, Q., Chou, J., Julé, A. M., Boudra, R., Contini, P., Crestani, E., Lai, P. S., Wang, M.-Y., Fong, J., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci163235 · Cited by 27 · see citing works
“We found upregulation of CD22, a member of the Siglec family of lectins normally found in B cells, where it acts to regulate B cell receptor signaling (45).”
Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy
Zhu, H.-B., Deng, H., Mu, J., Lyu, C., Jiang, Y.-Y., & Deng, Q. (2021) · OncoTargets and Therapy · doi:10.2147/ott.s312904 · Cited by 26
“Anti-CD22 CAR-T cell therapy provides a potential treatment strategy in addition to antiCD19 CAR-T cell therapy.(8,10,11) A study reported that anti-CD22 CAR-T cell therapy induced high response rates in R/R B-ALL patients whom had failed or relapsed again after a previous CD19 CAR-T cell therapy.”
Background
Development of Recombinant Immunotoxins for Hairy Cell Leukemia
Kreitman, R., & Pastan, I. (2020) · Biomolecules · doi:10.3390/biom10081140 · Cited by 25 · see citing works
Targeted Approaches to Inhibit Sialylation of Multiple Myeloma in the Bone Marrow Microenvironment
Natoni, A., Bohara, R., Pandit, A., & O'Dwyer, M. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00252 · Cited by 25 · see citing works
“Physiologically, ST6GAL1 is involved in the generation of CD22 ligands that control B cell functions (Clark and Giltiay, 2018).”
Background
Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk
Wang, X., Nissen, M. D., Gracias, D., Kusakabe, M., Simkin, G. O., Jiang, A., Duns, G., Sarkozy, C., Hilton, L. K., Chavez, E. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34408-0 · Cited by 36 · see citing works
Siglecs Modulate Activities of Immune Cells Through Positive and Negative Regulation of ROS Generation
Karmakar, J., Mukherjee, K., & Mandal, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.758588 · Cited by 24 · see citing works
Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome
Huang, L.-X., Qiao, Y., Xu, W., Gong, L., He, R., Qi, W.-L., Gao, Q.-C., Cai, H., Grossart, H., & Yan, Q.-P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.737332 · Cited by 24
Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses
Li, G., Ruan, S., Zhao, X., Liu, Q., Dou, Y., & Mao, F. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.11.056 · Cited by 24 · see citing works
“On the other hand, CD22, CCR6 and IL19 were found to be the top 3 hub genes in the turquoise module, and all these three genes are anti-inﬂammation genes and functionally important for preventing over-activation of the immune system and the development of autoimmune diseases [35-37] (Fig.”
Siglecs as modulators of macrophage phenotype and function
Kukan, E. N., Fabiano, G. L., & Cobb, B. A. (2024) · Seminars in Immunology · doi:10.1016/j.smim.2024.101887 · Cited by 24 · see citing works
Therapeutic Targets of Monoclonal Antibodies Used in the Treatment of Cancer: Current and Emerging
Effer, B. R., Perez, I., Ulloa, D., Mayer, C., Muñoz, F., Bustos, D., Rojas, C., Manterola, C., Vergara-Gómez, L., Dappolonnio, C., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11072086 · Cited by 28 · see citing works
“It is known to be an inhibitory receptor [126,127], and it is present exclusively on B cells, predominantly on mature B cells, where it regulates proliferation and function [128].”
Background
Bispecific CAR T-cells for B-cell Malignancies
Furqan, F., & Shah, N. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2086043 · Cited by 23 · see citing works
“● Targeting multiple agents may provide a benefit in preventing relapse due to antigen loss and treating CD19– relapse by simultaneously targeting two antigens expressed by B-cells.”
BackgroundInfluential
Inotuzumab ozogamicin in adult acute lymphoblastic leukemia: Development, current status, and future directions
Kantarjian, H., Boissel, N., Papayannidis, C., Luskin, M. R., Stelljes, M., Advani, A., Jabbour, E., Ribera, J., & Marks, D. I. (2024) · Cancer · doi:10.1002/cncr.35505 · Cited by 22
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“In addition, CD22 plays a key role in B cell responses and innate immunity (Clark and Giltiay 2018).”
Background

Authors: Clark, E. A., & Giltiay, N. V.
Affiliations: University of Washington (US)
Corresponding author: Clark, Edward A.
ORCID: Clark, Edward A.
Giltiay, Natalia V.
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2018-09-28
Volume: 9
Pages: 2235-2235
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2018.02235
PMC: PMC6173129
OpenAlex: W2893525181
Cited by: 197
References: 138
Citations by year: 2026: 24 · 2025: 29 · 2024: 28 · 2023: 31 · 2022: 35 · 2021: 23 · 2020: 20 · 2019: 7
FWCI: 1.28
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: Frontiers in Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Keywords: CD22, B cells, B cell signaling, innate immunity, adaptive immunity, autoimmunity, systemic lupus erythematosus, immunotherapeutics, Siglec-G
MeSH terms: Alleles, Animals, Autoantibodies, B-Lymphocytes, Humans, Receptors, Antigen, B-Cell, Autoimmunity, Polymorphism, Single Nucleotide, Toll-Like Receptor 7, Mice, Sialic Acid Binding Ig-like Lectin 2, Molecular Targeted Therapy

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CD22: A Regulator of Innate and Adaptive B Cell Responses and Autoimmunity

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