BAFF-driven autoimmunity requires CD19 expression.

Autor: Fairfax KA; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia; The Walter and Eliza Hall Institute of Medical Research, Molecular Medicine Division, 1G Royal Parade, Melbourne 3052, Australia; The Department of Experimental Medicine, University of Melbourne, Parkville, Victoria 3052, Australia., Tsantikos E; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia., Figgett WA; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia., Vincent FB; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia., Quah PS; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia., LePage M; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia., Hibbs ML; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia., Mackay F; Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia. Electronic address: Fabienne.Mackay@monash.edu.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2015 Aug; Vol. 62, pp. 1-10. Date of Electronic Publication: 2015 Jun 20.
DOI: 10.1016/j.jaut.2015.06.001
Abstrakt: 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.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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