B cell maturation antigen deficiency exacerbates lymphoproliferation and autoimmunity in murine lupus.

Systemic lupus erythematosus and its preclinical lupus-prone mouse models are autoimmune disorders involving the production of pathogenic autoantibodies. Genetic predisposition to systemic lupus erythematosus results in B cell hyperactivity, survival of self-reactive B cells, and differentiation to autoantibody-secreting plasma cells (PCs). These corrupt B cell responses are, in part, controlled by excess levels of the cytokine BAFF that normally maintains B cell homeostasis and self-tolerance through limited production. B cell maturation Ag (BCMA) is a receptor for BAFF that, under nonautoimmune conditions, is important for sustaining enduring Ab protection by mediating survival of long-lived PCs but is not required for B cell maturation and homeostasis. Through analysis of two different lupus-prone mouse models deficient in BCMA, we identify BCMA as an important factor in regulating peripheral B cell expansion, differentiation, and survival. We demonstrate that a BCMA deficiency combined with the lpr mutation or the murine lupus susceptibility locus Nba2 causes dramatic B cell and PC lymphoproliferation, accelerated autoantibody production, and early lethality. This study unexpectedly reveals that BCMA works to control B cell homeostasis and self-tolerance in systemic autoimmunity.

Citation

Chao Jiang, William M Loo, Erin J Greenley, Kenneth S Tung, Loren D Erickson. B cell maturation antigen deficiency exacerbates lymphoproliferation and autoimmunity in murine lupus. Journal of immunology (Baltimore, Md. : 1950). 2011 Jun 1;186(11):6136-47

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PMID: 21536804

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