| First Author | Olalekan SA | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 4 | Pages | 988-98 |
| PubMed ID | 25645456 | Mgi Jnum | J:229645 |
| Mgi Id | MGI:5752718 | Doi | 10.1002/eji.201445036 |
| Citation | Olalekan SA, et al. (2015) B cells expressing IFN-gamma suppress Treg-cell differentiation and promote autoimmune experimental arthritis. Eur J Immunol 45(4):988-98 |
| abstractText | 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 naive CD4(+) T cells into Treg cells. Since the development of PGIA is dependent on IFN-gamma and B cells are reported to produce IFN-gamma, we hypothesized that B-cell-specific IFN-gamma plays a role in the development of PGIA. Accordingly, mice with B-cell-specific IFN-gamma deficiency were as resistant to the induction of PGIA as mice that were completely IFN-gamma deficient. Importantly, despite a normal frequency of IFN-gamma-producing CD4(+) T cells, B-cell-specific IFN-gamma-deficient mice exhibited a higher percentage of Treg cells compared with that in WT mice. These data indicate that B-cell IFN-gamma production inhibits Treg-cell differentiation and exacerbates arthritis. Thus, we have established that IFN-gamma, specifically derived from B cells, uniquely contributes to the pathogenesis of autoimmunity through prevention of immunoregulatory mechanisms. |
