FcR-like 2 Inhibition of B cell receptor-mediated activation of B cells

J Immunol. 2010 Dec 15;185(12):7405-12. doi: 10.4049/jimmunol.1002305. Epub 2010 Nov 10.

Abstract

FcR-like (FCRL) 2 is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus ITIMs in addition to a putative ITAM sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and analyzed its functional potential to show that coligation with the BCR leads to tyrosine phosphorylation of its ITIM motifs and subsequent Src homology region 2 domain-containing phosphatase-1 recruitment to facilitate inhibition of BCR signaling. Mutational analysis indicates that the tyrosine residues in both inhibitory motifs of FCRL2 are required for complete inhibition of BCR signaling, whereas tyrosines in the putative activation motif are dispensable for signal modulation. These findings suggest a negative immunomodulatory function for FCRL2 in the regulation of memory B cells.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Substitution
  • Animals
  • B-Lymphocytes / immunology*
  • Cell Line
  • Humans
  • Immunologic Memory / physiology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Mutation
  • Phosphorylation / genetics
  • Phosphorylation / immunology
  • Protein Structure, Tertiary
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*

Substances

  • FCRL2 protein, human
  • Receptors, Antigen, B-Cell
  • Receptors, Cell Surface