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BAFF-driven autoimmunity requires CD19 expression
Citation
Fairfax, KA and Tsantikos, E and Figgett, WA and Vincent, FB and Quah, PS and LePage, M and Hibbs, ML and Mackay, F, BAFF-driven autoimmunity requires CD19 expression, Journal of Autoimmunity, 62 pp. 1-10. ISSN 0896-8411 (2015) [Refereed Article]
Copyright Statement
Copyright 2015 Elsevier Ltd.
DOI: doi:10.1016/j.jaut.2015.06.001
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | autoimmunity, B1b cells, BAFF, BAFF-transgenic, CD19, MZ B cells |
| Research Division: | Biological Sciences |
| Research Group: | Biochemistry and Cell Biology |
| Research Field: | Cell Development, Proliferation and Death |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Immune System and Allergy |
| UTAS Author: | Fairfax, KA (Dr Kirsten Fairfax) |
| ID Code: | 134780 |
| Year Published: | 2015 |
| Web of Science® Times Cited: | 17 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2019-09-04 |
| Last Modified: | 2019-10-16 |
| Downloads: | 0 |
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