AUTHOR=Yao Yunliang , Huang Wei , Li Xiaoyu , Li Xiawei , Qian Jin , Han Hui , Sun Hui , An Xiangli , Lu Linrong , Zhao Hongxing 

TITLE=Tespa1 Deficiency Dampens Thymus-Dependent B-Cell Activation and Attenuates Collagen-Induced Arthritis in Mice

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00965

DOI=10.3389/fimmu.2018.00965

ISSN=1664-3224

ABSTRACT=<p>Thymocyte-expressed, positive selection-associated 1 (<italic>Tespa1</italic>) plays an important role in both T cell receptor (TCR)-driven thymocyte development and in the FcεRI-mediated activation of mast cells. Herein, we show that lack of <italic>Tespa1</italic> does not impair B cell development but dampens the <italic>in vitro</italic> activation and proliferation of B cells induced by T cell-dependent (TD) antigens, significantly reduces serum antibody concentrations <italic>in vivo</italic>, and impairs germinal center formation in both aged and TD antigen-immunized mice. We also provide evidence that dysregulated signaling in <italic>Tespa1</italic>-deficient B cells may be linked to CD40-induced TRAF6 degradation, and subsequent effects on 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2) phosphorylation, MAPK activation, and calcium influx. Furthermore, we demonstrate that <italic>Tespa1</italic> plays a critical role in pathogenic B cells, since <italic>Tespa1</italic>-deficient chimeric mice showed a lower incidence and clinical disease severity of collagen-induced arthritis. Overall, our study demonstrates that <italic>Tespa1</italic> is essential for TD B cell responses, and suggests an important role for <italic>Tespa1</italic> during the development of autoimmune arthritis.</p>