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Cited by 578Systemic Lupus Erythematosus ResearchT-cell and B-cell ImmunologySystemic Sclerosis and Related Diseases

IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE

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Wang, Shu, Wang, Jingya, Kumar, Varsha, Karnell, Jodi L., Naiman, Brian, Gross, Phillip S., Rahman, Saifur, Zerrouki, Kamelia +24 more·2018·Nature Communications
DOI 10.1038/s41467-018-03750-7PMC PMC5931508
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Abstract

Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11c hi T-bet + B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11c hi T-bet + B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells. While murine studies have identified a role for T-bet-expressing B cells in autoimmunity, this study describes and exemplifies the importance of CD11c hi T-bet + B cells in human SLE.

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  • ABCs are characterized in mice by the surface phenotype CD19+, CD11c+, T-bet+, CD11b+, CD21-, CD23-, CD86+, MHCII+, and in humans by CD11c+, T-bet+, CD27-, IgD-, CD38-, CD21-.

    “They are charac­ terized in mice by the surface phenotype CD19 + , CD11c + , T-bet + , CD11b + , CD21 , CD23 , CD86 + , MHCII + , and in humans by CD11c + , Tbet + , CD27 , IgD , CD38 , CD21 [69 -72].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [72]

    The Introduction and Results (Phenotypes of CD11chi B cells from SLE patients; page unavailable) support several listed markers: murine ABCs express CD11c and T-bet, and the paper describes murine CD11b+CD21−CD23− cells and human CD11chiT-bet+CD21− cells with low CD27 and CD38. But it does not establish the full murine surface-marker list, including CD86+ and MHCII+, and it explicitly reports that a fraction of the human cells express IgD rather than being uniformly IgD−. (LLM, conf=0.88)

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Authors
Wang, S., Wang, J., Kumar, V., Karnell, J. L., Naiman, B., Gross, P. S., Rahman, S., Zerrouki, K., Hanna, R., Morehouse, C., Holoweckyj, N., Liu, H., Autoimmunity Molecular Medicine Team, Casey, K., Smith, M., Parker, M., White, N., Riggs, J., Ward, B., Bhat, G., Rajan, B., Grady, R., Groves, C., Manna, Z., Goldbach-Mansky, R., Hasni, S., Siegel, R., Sanjuan, M., Streicher, K., Cancro, M. P., Kolbeck, R., & Ettinger, R.
Affiliations
  • National Institutes of Health (US)
  • University of Pennsylvania (US)
  • National Institute of Standards and Technology (US)
Corresponding author
Ettinger, Rachel
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-05-01
Volume
9
Issue
1
Pages
1758-1758
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-03750-7
PMC
PMC5931508
OpenAlex
W2805930941
Cited by
578
References
4
Citations by year
2026: 70 · 2025: 76 · 2024: 80 · 2023: 78 · 2022: 72 · 2021: 76 · 2020: 54 · 2019: 58 · 2018: 13
FWCI
43.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Texas Southwestern Medical Center
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R01AI118691)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
Keywords
systemic lupus erythematosus, IL-21, autoreactive B cells, plasma cell differentiation, B cell expansion, chemokine receptors, B cell migration, autoimmunity, T-bet
MeSH terms
Interleukin-21, Adult, Aged, Aged, 80 and over, B-Lymphocytes, Cell Differentiation, Female, Humans, Interleukins, Lupus Erythematosus, Systemic, Male, Middle Aged, Plasma Cells, Cohort Studies, B-Lymphocyte Subsets, T-Box Domain Proteins, CD11c Antigen, Young Adult

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