BAFF-driven autoimmunity requires CD19 expression
- Author(s)
- Fairfax, KA; Tsantikos, E; Figgett, WA; Vincent, FB; Quah, PS; LePage, M; Hibbs, ML; Mackay, F;
- Journal Title
- J Autoimmun
- Publication Type
- Journal Article
- Abstract
- B 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.
- Publisher
- Elsevier
- Research Division(s)
- Molecular Medicine
- PubMed ID
- 26103922
- Publisher's Version
- https://doi.org/10.1016/j.jaut.2015.06.001
- NHMRC Grants
- NHMRC/1008520, NHMRC/1016953, NHMRC/516786, NHMRC/1020630, NHMRC/603124,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-09-01 03:55:18
Last Modified: 2015-09-02 02:55:16