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

Front Immunol. 2018 May 14:9:965. doi: 10.3389/fimmu.2018.00965. eCollection 2018.

Abstract

Thymocyte-expressed, positive selection-associated 1 (Tespa1) 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 Tespa1 does not impair B cell development but dampens the in vitro activation and proliferation of B cells induced by T cell-dependent (TD) antigens, significantly reduces serum antibody concentrations in vivo, and impairs germinal center formation in both aged and TD antigen-immunized mice. We also provide evidence that dysregulated signaling in Tespa1-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 Tespa1 plays a critical role in pathogenic B cells, since Tespa1-deficient chimeric mice showed a lower incidence and clinical disease severity of collagen-induced arthritis. Overall, our study demonstrates that Tespa1 is essential for TD B cell responses, and suggests an important role for Tespa1 during the development of autoimmune arthritis.

Keywords: B-cell; CD40; PLCG2; collagen-induced arthritis; tespa1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / immunology*
  • Autoimmunity
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • CD40 Antigens / immunology
  • Calcium / metabolism
  • Collagen / administration & dosage*
  • Germinal Center / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phospholipase C gamma / metabolism
  • Phosphorylation
  • Signal Transduction
  • T-Lymphocytes / immunology
  • TNF Receptor-Associated Factor 6 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CD40 Antigens
  • TNF Receptor-Associated Factor 6
  • Tespa1 protein, mouse
  • Collagen
  • Phospholipase C gamma
  • Calcium