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BAFF-driven autoimmunity requires CD19 expression
journal contribution
posted on 2023-05-20, 06:52 authored by Kirsten FairfaxKirsten Fairfax, Tsantikos, E, Figgett, WA, Vincent, FB, Quah, PS, LePage, M, Hibbs, ML, Mackay, FB cell activating factor of the tumor necrosis factor family (BAFF or BLyS) is a critical factor for B cell survival and maturation. BAFF-transgenic (BAFF-Tg) mice develop autoimmunity that resembles systemic lupus erythematosus (SLE) in a T cell-independent but MyD88-dependent manner, implicating toll-like receptor (TLR) signaling. The specific B cell subtypes that make pro-inflammatory autoantibodies in BAFF-Tg mice are TLR-activated innate B cells known as marginal zone (MZ) and B1 B cells. These cells infiltrate the salivary glands and kidneys of diseased BAFF-Tg mice. However, loss of B1a or MZ B cells does not protect BAFF-Tg mice against disease, suggesting that B1b B cells might be the important pathogenic B cell subset. To test this hypothesis, we have generated BAFF-Tg mice that retained follicular B cells, but are deficient in B1a, B1b and MZ B cells, by crossing BAFF-Tg mice to CD19-deficient mice (BTg-CD19(-/-)). The BTg-CD19(-/-) mice did not produce autoantibodies and were protected from splenomegaly, kidney pathology and all signs of autoimmunity. This work suggests that B1b B cells, rather than MZ or B1a B cells, are sufficient and possibly required for the development of autoimmunity. Loss of the majority of innate-like B cells was able to protect BAFF-Tg mice from developing disease, so we can now conclude that autoimmunity induced by excessive BAFF production requires B1b B cells and CD19 signaling.
History
Publication title
Journal of AutoimmunityVolume
62Pagination
1-10ISSN
0896-8411Department/School
Menzies Institute for Medical ResearchPublisher
Academic Press Ltd Elsevier Science LtdPlace of publication
24-28 Oval Rd, London, England, Nw1 7DxRights statement
Copyright 2015 Elsevier Ltd.Repository Status
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