title: B cell maturation antigen deficiency exacerbates lymphoproliferation and autoimmunity in murine lupus.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.forename: William M
authors.initials: WM
authors.lastname: Loo
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Greenley
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Tung
authors.forename: Loren D
authors.initials: LD
authors.lastname: Erickson
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000172:deficiency* / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D053208:Kaplan-Meier Estimate; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; C505720:Tnfsf13b protein, mouse