title: B cells expressing IFN-γ suppress Treg-cell differentiation and promote autoimmune experimental arthritis.
abstract: Clinical efficacy in the treatment of rheumatoid arthritis with anti-CD20 (Rituximab)-mediated B-cell depletion has garnered interest in the mechanisms by which B cells contribute to autoimmunity. We have reported that B-cell depletion in a murine model of proteoglycan-induced arthritis (PGIA) leads to an increase in Treg cells that correlate with decreased autoreactivity. Here, we demonstrate that the increase in Treg cells after B-cell depletion is due to an increase in the differentiation of naïve CD4(+) T cells into Treg cells. Since the development of PGIA is dependent on IFN-γ and B cells are reported to produce IFN-γ, we hypothesized that B-cell-specific IFN-γ plays a role in the development of PGIA. Accordingly, mice with B-cell-specific IFN-γ deficiency were as resistant to the induction of PGIA as mice that were completely IFN-γ deficient. Importantly, despite a normal frequency of IFN-γ-producing CD4(+) T cells, B-cell-specific IFN-γ-deficient mice exhibited a higher percentage of Treg cells compared with that in WT mice. These data indicate that B-cell IFN-γ production inhibits Treg-cell differentiation and exacerbates arthritis. Thus, we have established that IFN-γ, specifically derived from B cells, uniquely contributes to the pathogenesis of autoimmunity through prevention of immunoregulatory mechanisms.
authors: Department of Immunology/Microbiology, Rush University Medical Center, Cohn Research Building, Chicago, IL, USA.
authors: Susan A
authors: SA
authors: Olalekan
authors: Yanxia
authors: Y
authors: Cao
authors: Keith M
authors: KM
authors: Hamel
authors: Alison
authors: A
authors: Finnegan
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D053674:Aggrecans / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D051858:Forkhead Transcription Factors / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D000069283:Rituximab; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D053674:Aggrecans; D058846:Antibodies, Monoclonal, Murine-Derived; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; D000069283:Rituximab; D007371:Interferon-gamma
keywords: Arthritis; Autoimmunity; B cells; IFN-γ; Treg cells
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