CoChat
Sign Up
Cited by 16Monoclonal and Polyclonal Antibodies ResearchT-cell and B-cell ImmunologyProtein Structure and Dynamics

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

CD5L associates with IgM via the J chain

Open access
Wang, Yuxin, Su, Chen, Ji, Chenggong, Xiao, Junyu·2024·Nature Communications
DOI 10.1038/s41467-024-52175-yPMC PMC11437284

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Abstract CD5 antigen-like (CD5L), also known as Spα or AIM (Apoptosis inhibitor of macrophage), emerges as an integral component of serum immunoglobulin M (IgM). However, the molecular mechanism underlying the interaction between IgM and CD5L has remained elusive. In this study, we present a cryo-electron microscopy structure of the human IgM pentamer core in complex with CD5L. Our findings reveal that CD5L binds to the joining chain (J chain) in a Ca2+-dependent manner and further links to IgM via a disulfide bond. We further show that CD5L reduces IgM binding to the mucosal transport receptor pIgR, but does not impact the binding of the IgM-specific receptor FcμR. Additionally, CD5L does not interfere with IgM-mediated complement activation. These results offer new insights into our understanding of IgM and shed new light on the function of the J chain in the immune system.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-024-52175-y

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 47

  1. Heidelberger, M. & Pedersen, K. O. The molecular weight of antibodies. J. Exp. Med. 65, 393–414 (1937). · DOI
  2. Tissot, J. D., Hochstrasser, D. F., Spertini, F., Schifferli, J. A. & Schneider, P. Pattern variations of polyclonal and monoclonal immunoglobulins of different isotypes analyzed by high‐resolution two‐dimensional electrophoresis. Electrophoresis 14, 227–234 (1993). · DOI
  3. Tissot, J. D. et al. Two-dimensional polyacrylamide gel electrophoresis analysis of cryoglobulins and identification of an IgM-associated peptide. J. Immunol. Methods 173, 63–75 (1994). · DOI
  4. Gebe, J. A. et al. Molecular cloning, mapping to human chromosome 1 q21-q23, and cell binding characteristics of Spα, a new member of the scavenger receptor cysteine-rich (SRCR) family of proteins. J. Biol. Chem. 272, 6151–6158 (1997). · DOI
  5. Miyazaki, T., Hirokami, Y., Matsuhashi, N., Takatsuka, H. & Naito, M. Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily. J. Exp. Med. 189, 413–422 (1999). · DOI
  6. Gebe, J. A., Llewellyn, M., Hoggatt, H. & Aruffo, A. Molecular cloning, genomic organization and cell-binding characteristics of mouse Spalpha. Immunology 99, 78–86 (2000). · DOI
  7. Tissot, J. D. et al. IgM are associated to Spα (CD5 antigen‐like). Electrophoresis 23, 1203–1206 (2002). · DOI
  8. Oskam, N. et al. CD5L is a canonical component of circulatory IgM. Proc. Natl Acad. Sci. USA 120, e2311265120 (2023). · DOI
  9. Sanjurjo, L., Aran, G., Roher, N., Valledor, A. F. & Sarrias, M. R. AIM/CD5L: a key protein in the control of immune homeostasis and inflammatory disease. J. Leukoc. Biol. 98, 173–184 (2015). · DOI
  10. Miyazaki, T., Yamazaki, T., Sugisawa, R., Gershwin, M. E. & Arai, S. AIM associated with the IgM pentamer: attackers on stand-by at aircraft carrier. Cell. Mol. Immunol. 15, 563–574 (2018). · DOI
  11. Joseph, S. B. et al. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119, 299–309 (2004). · DOI
  12. Sarrias, M.-R. et al. A role for human Spα as a pattern recognition receptor. J. Biol. Chem. 280, 35391–35398 (2005). · DOI
  13. Martinez, V. G. et al. The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression. Cell. Mol. Immunol. 11, 343–354 (2014). · DOI
  14. Gao, X., Yan, X. X., Zhang, Q., Yin, Y. B. & Cao, J. CD5L contributes to the pathogenesis of methicillin-resistant Staphylococcus aureus-induced pneumonia. Int. Immunopharmacol. 72, 40–47 (2019). · DOI
  15. Maehara, N. et al. AIM/CD5L attenuates DAMPs in the injured brain and thereby ameliorates ischemic stroke. Cell Rep. 36, 109693 (2021). · DOI
  16. Arai, S. et al. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice. Nat. Med. 22, 183–193 (2016). · DOI
  17. Maehara, N. et al. Circulating AIM prevents hepatocellular carcinoma through complement activation. Cell Rep. 9, 61–74 (2014). · DOI
  18. Kuwata, K. et al. AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice. Am. J. Pathol. 162, 837–847 (2003). · DOI
  19. Li, J. J., Lin, W. & Zhuang, L. CD5L-induced activation of autophagy is associated with hepatoprotection in ischemic reperfusion injury via the CD36/ATG7 axis. Exp. Ther. Med. 19, 2588–2596 (2020).
  20. Wang, C. et al. CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity. Cell 163, 1413–1427 (2015). · DOI
  21. Kurokawa, J. et al. Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity. Cell Metab. 11, 479–492 (2010). · DOI
  22. Arai, S. et al. A role for the apoptosis inhibitory factor AIM/Spα/Api6 in atherosclerosis development. Cell Metab. 1, 201–213 (2005). · DOI
  23. Takahata, A. et al. Crucial role of AIM/CD5L in the development of glomerular inflammation in IgA nephropathy. J. Am. Soc. Nephrol. 31, 2013–2024 (2020). · DOI
  24. Oliveira, L. et al. CD5L as a promising biological therapeutic for treating sepsis. Nat. Commun. 15, 4119 (2024). · DOI
  25. Resnick, D., Pearson, A. & Krieger, M. The SRCR superfamily: a family reminiscent of the Ig superfamily. Trends Biochem. Sci. 19, 5–8 (1994). · DOI
  26. Sarrias, M. R. et al. The scavenger receptor cysteine-rich (SRCR) domain: an ancient and highly conserved protein module of the innate immune system. Crit. Rev. Immunol. 24, 1–37 (2004). · DOI
  27. Reichhardt, M. P., Loimaranta, V., Lea, S. M. & Johnson, S. Structures of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR fold. Life Sci. Alliance 3, e201900502 (2020). · DOI
  28. Sugisawa, R. et al. Impact of feline AIM on the susceptibility of cats to renal disease. Sci. Rep. 6, 35251 (2016). · DOI
  29. Hiramoto, E. et al. The IgM pentamer is an asymmetric pentagon with an open groove that binds the AIM protein. Sci. Adv. 4, eaau1199 (2018). · DOI
  30. Sharp, T. H. et al. Insights into IgM-mediated complement activation based on in situ structures of IgM-C1-C4b. Proc. Natl Acad. Sci. USA 116, 11900–11905 (2019). · DOI
  31. Li, Y. X. et al. Structural insights into immunoglobulin M. Science 367, 1014–1017 (2020). · DOI
  32. Kumar, N., Arthur, C. P., Ciferri, C. & Matsumoto, M. L. Structure of the human secretory immunoglobulin M core. Structure 29, 564–571 e3 (2021). · DOI
  33. Chen, Q., Menon, R., Calder, L. J., Tolar, P. & Rosenthal, P. B. Cryomicroscopy reveals the structural basis for a flexible hinge motion in the immunoglobulin M pentamer. Nat. Commun. 13, 6314 (2022). · DOI
  34. Kumar, N., Arthur, C. P., Ciferri, C. & Matsumoto, M. L. Structure of the secretory immunoglobulin A core. Science 367, 1008–1014 (2020). · DOI
  35. Wang, Y. X. et al. Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin. Cell Res. 30, 602–609 (2020). · DOI
  36. Bharathkar, S. K. et al. The structures of secretory and dimeric immunoglobulin A. Elife 9, e56098 (2020). · DOI
  37. Kubagawa, H. et al. Identity of the elusive IgM Fc receptor (FcmuR) in humans. J. Exp. Med. 206, 2779–2793 (2009). · DOI
  38. Li, Y. et al. Immunoglobulin M perception by FcmuR. Nature 615, 907–912 (2023). · DOI
  39. Shibuya, A. et al. Fc alpha/mu receptor mediates endocytosis of IgM-coated microbes. Nat. Immunol. 1, 441–446 (2000). · DOI
  40. Arya, S. et al. Mapping of amino acid residues in the C mu 3 domain of mouse IgM important in macromolecular assembly and complement-dependent cytolysis. J. Immunol. 152, 1206–1212 (1994). · DOI
  41. Ji, C. et al. Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M. Nat. Commun. 14, 2650 (2023). · DOI
  42. Koshland, M. E. The coming of age of the immunoglobulin J chain. Annu Rev. Immunol. 3, 425–453 (1985). · DOI
  43. Su, C., Wang, Y., Yang, X. & Xiao, J. J chain dictates the recognition of IgA by FcRL4. bioRxiv 12, 572144 (2023). 202318.
  44. Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017). · DOI · Paper page
  45. Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021). · DOI
  46. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. Sect. D 66, 486–501 (2010). · DOI · Paper page
  47. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. Sect. D 66, 213–221 (2010). · DOI · Paper page

Metadata

Authors
Wang, Y., Su, C., Ji, C., & Xiao, J.
Affiliations
Peking University (CN)
Corresponding author
Xiao, Junyu
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-09-27
Volume
15
Issue
1
Pages
8397-8397
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-52175-y
PMC
PMC11437284
OpenAlex
W4402903351
Cited by
16
References
1
Citations by year
2026: 11 · 2025: 4 · 2024: 1
FWCI
4.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Greater South Information System
Funders
  • National Natural Science Foundation of China (32325018)
  • Qidong-SLS Innovation Fund Changping Laboratory
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
CD5L, AIM, IgM pentamer, J chain, polymeric immunoglobulin receptor, FcμR, complement activation, calcium-dependent binding, disulfide bonds, serum immunoglobulin M, protein-protein interaction, cryo-EM structure
MeSH terms
Calcium, Humans, Immunoglobulin M, Immunoglobulin J-Chains, Protein Binding, Cryoelectron Microscopy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review