Themis2 is not required for B cell development, activation, and antibody responses

J Immunol. 2014 Jul 15;193(2):700-7. doi: 10.4049/jimmunol.1400943. Epub 2014 Jun 6.

Abstract

Themis1 is a protein implicated in transducing signals from the TCR. Mice deficient in Themis1 show a strong impairment in T cell selection in the thymus and defective T cell activation. The related Themis2 protein is expressed in B cells where it associates with signaling proteins Grb2 and Vav1, and is tyrosine phosphorylated after BCR stimulation. Thus, it has been proposed that Themis2 may transduce BCR signals, and hence play important roles in B cell development and activation. In this article, we show that Themis2 is expressed in all developing subsets of B cells, in mature follicular and marginal zone B cells, and in activated B cells, including germinal center B cells and plasma cells. In contrast, B lineage cells express no other Themis-family genes. Activation of B cells leads to reduced Themis2 expression, although it remains the only Themis-family protein expressed. To analyze the physiological function of Themis2, we generated a Themis2-deficient mouse strain. Surprisingly, we found that Themis2 is not required for B cell development, for activation, or for Ab responses either to model Ags or to influenza viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / immunology*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Bone Marrow / immunology
  • Bone Marrow / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression / immunology
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Themis2 protein, mouse