The Role of Fc receptor‐like 2 in B cell Signaling

Abstract

The Fc receptor‐like protein 2 (FCRL2) is a member of a family of receptors identified on the basis of sequence similarity with previously identified Fc receptors. The human FCRL2 transmembrane protein has 4 Ig‐like extracellular domains and a cytoplasmic tail containing one potential ITAM (immunoreceptor tyrosine‐based activation motif) and two ITIMs (immunoreceptor tyrosine‐based inhibitory motifs). To define its signaling potential in B cells, we constructed a chimeric receptor containing the extracellular and transmembrane domain of FcγRIIb fused to the intracellular domain of FCRL2 and expressed it in an Fc receptor deficient B cell line. Our functional analysis shows that, when coligated with the B cell receptor (BCR) by intact antibody, the FcγRIIb‐FCRL2 chimeric receptor is tyrosine phosphorylated, recruits the SHP‐1 phosphatase, and inhibits whole cell tyrosine phosphorylation. Preliminary data suggest that ERK activation and calcium mobilization are also inhibited upon crosslinking of FCRL2 with the BCR. These results indicate that FCRL2 may serve an inhibitory function in B cells.NIH/NIAID 5 T32 AI07051; 5 T32 GM08111‐20