FCRL is Fc Receptor-Like protein and is a subfamily of five Ig superfamily members. FCRL is also called Fc Receptor Homolog (FCRH). The genes of FCRLs locate on human chromosome 1 and mouse chromosome 3. The genes of FCRLs have also been identified as immunoglobulin superfamily receptor translocation associated (IRTA) genes, SH-2 domain-containing phosphatase anchor proteins (SPAP) genes. FCRLs have sequence homology with the classical Fc receptor for IgG, FccRI, FccRII and FccRIII. Members of FcRH1–5 subfamily belong to the network of receptors that possess immunoreceptor tyrosinebased activating motifs (ITAM), inhibition motifs (ITIM) or both. Their functions are as an activating coreceptor in B-cells and promoting B-cells activation and differentiation.
FCRL1 expression begins in pre-B cells, reaches peak levels on naive B cells and is downregulated when B cells are activated to form germinal centers. This FCRL1 down-regulation coincides with dramatic enlargement of the pre-germinal center cells, cell cycle entry and other overt signs of activation that include CD80 and CD86 up-regulation and immunoglobulin D (IgD) down-regulation. In vitro analysis indicates that ligation of FcRH1 leads to its tyrosine phosphorylation and to modest B-cell activation and proliferation.
FCRL1 is an intrinsic activation molecule that has the potential to augment BCR-induced activation. FCRL1 has significant activation potential and may serve as an activation coreceptor on B cells. Cross-linkage of FCRL1 alone stimulates its tyrosine phosphorylation. FCRL1 ligation also induces a modest increase in B-cell size, enhances CD69 and CD86 expression, and decreases cell surface IgD levels.