General autoimmunity

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Role and Regulation of CD11chi T-bet+ B cells in SLE

Thursday, June 15
3:39 PM - 3:52 PM

We examined a large cohort of systemic lupus erythematosus (SLE) patients and found an unusual B cell subset highly expanded. These B cells displayed a unique phenotype and expressed antigens not present on other B cell populations, including high densities of CD11c, FcRL5, and the T-box transcription factor, T-bet, but unexpectedly, were CD40lo and CD24-. Although these CD11chi cells were largely negative for the memory B cell antigen CD27, their telomere length was consistent with memory, rather than naïve B cells. Notably, the increase of CD11chi B cells in SLE significantly correlated with disease severity scores as well as with other markers of disease activity including serum IL-21. While memory B cells characteristically express low densities of IL-21R, these memory CD11chi B cells were IL-21R bright. In culture, IL-21 was a potent driver of CD11c expression when B cells were co-stimulated through the B cell receptor and CD40. Lastly, CD11chi B cells in SLE significantly correlated with blood plasma cells as well as a distinct set of autoantibodies, and importantly, were efficiently driven to differentiate into plasma cells in response to activated T cells. These data indicate that among the many roles of IL-21 in regard to B cell activation and differentiation, this pleiotropic cytokine also regulates CD11chi B cells, and presumably contributes to autoimmunity through the differentiation of autoreactive CD11chi B cells in SLE.

Shu Wang

Medimmune LLC

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Jingya Wang

Medimmune

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Varsha Kumar

Medimmune

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Brian Naiman

Medimmune

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Jodi Karnell

Medimmune

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Phillip Gross

summer intern
Medimmune

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Saifur Rahman

Medimmune

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Zerai Manna

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health

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Sarfaraz Hasni

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health

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Richard Siegel

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health

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Miguel Sanjuan

Medimmune

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Michael Cancro

Perelman School of Medicine, University of Pennsylvania

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Roland Kolbeck

Medimmune

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Rachel Ettinger

Medimmune

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Role and Regulation of CD11chi T-bet+ B cells in SLE



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