FCRL5 exerts binary and compartment-specific influence on innate-like B-cell receptor signaling

Academic Article

Abstract

  • Innate-like splenic marginal zone (MZ) and peritoneal cavity B1 B lymphocytes share critical responsibilities in humoral responses but have divergent B-cell receptor (BCR) signaling features. A discrete marker of these subsets with tyrosine-based dual regulatory potential termed "Fc receptor-like 5" (FCRL5) was investigated to explore this discrepancy. Although FCRL5 repressed the robust BCR activity that is characteristic of MZ B cells, it had no influence on antigen receptor stimulation that is blunted in peritoneal cavityderived B1 B cells. The molecular basis for the receptor's inhibitory function derived from recruitment of the Src homology-2 domaincontaining tyrosine phosphatase 1 (SHP-1) to a cytoplasmic immunoreceptor tyrosine-based inhibitory motif. Surprisingly, mutagenesis of this docking site unearthed coactivation properties for FCRL5 that were orchestrated by independent association of the Lyn Src-family kinase with an intracellular immunoreceptor tyrosine- based activation motif-like sequence. FCRL5's unique binary regulation directly correlated with SHP-1 and Lyn activity, which, like BCR function, differed between MZ and B1 B cells. These findings collectively imply a specialized counterregulatory role for FCRL molecules at the intersection of innate and adaptive immunity.
  • Digital Object Identifier (doi)

    Author List

  • Zhu Z; Li R; Li H; Zhou T; Davis RS
  • Volume

  • 110
  • Issue

  • 14