The Small Rho GTPase TC10 Modulates B Cell Immune Responses

J Immunol. 2017 Sep 1;199(5):1682-1695. doi: 10.4049/jimmunol.1602167. Epub 2017 Jul 26.

Abstract

Rho family GTPases regulate diverse cellular events, such as cell motility, polarity, and vesicle traffic. Although a wealth of data exists on the canonical Rho GTPases RhoA, Rac1, and Cdc42, several other family members remain poorly studied. In B cells, we recently demonstrated a critical role for Cdc42 in plasma cell differentiation. In this study, we focus on a close homolog of Cdc42, TC10 (also known as RhoQ), and investigate its physiological role in B cells. By generating a TC10-deficient mouse model, we show that despite reduced total B cell numbers, B cell development in these mice occurs normally through distinct developmental stages. Upon immunization, IgM levels were reduced and, upon viral infection, germinal center responses were defective in TC10-deficient mice. BCR signaling was mildly affected, whereas cell migration remained normal in TC10-deficient B cells. Furthermore, by generating a TC10/Cdc42 double knockout mouse model, we found that TC10 can compensate for the lack of Cdc42 in TLR-induced cell activation and proliferation, so the two proteins play partly redundant roles. Taken together, by combining in vivo and in vitro analysis using TC10-deficient mice, we define the poorly studied Rho GTPase TC10 as an immunomodulatory molecule playing a role in physiological B cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Germinal Center / immunology
  • Immunomodulation
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction
  • Vaccinia / immunology*
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Cdc42 protein, mouse
  • Receptors, Antigen, B-Cell
  • Rhoq protein, mouse
  • cdc42 GTP-Binding Protein
  • rho GTP-Binding Proteins