Abstract
Members of the family of Fc receptor-like (FcRL) proteins, homologous to FcγRI, have been identified by multiple research groups. Consequently, they have been described using multiple nomenclatures including Fc receptor homologs (FcRH), immunoglobulin superfamily receptor translocation-associated genes (IRTA), immunoglobulin-Fc-gp42-related genes (IFGP), Src homology 2 domain-containing phosphatase anchor proteins (SPAP), and B cell cross-linked by anti-immunoglobulin M-activating sequences (BXMAS). They are now referred to under a unified nomenclature as FCRL. Eight different human FCRL genes have been identified, all of which appear to be related to the genes of the immunoglobulin superfamily (IgSF) of cellular adhesion molecules. These type 1 transmembrane glycoproteins are composed of different combinations of 5 types of immunoglobulin-like domains, with each protein consisting of 3 to 9 domains, and no individual domain type conserved throughout all of the FCRL proteins. Ligands for the majority of the FCRLs remain unknown. In general, FCRL expression is restricted to lymphocytes and is primarily expressed in B-lymphocytes, supporting FCRL's involvement in a variety of immune disorders. Most FCRLs functionally repress B-cell activation; however, they might have dual roles in lymphocyte functions as these proteins often possess immunoreceptor tyrosine activation (ITAM) and inhibitory (ITIM) motif elements. The biological functions of these newly recognized FCRL proteins are just beginning to emerge, and might provide the insight necessary for understanding pathophysiology of lymphocyte disorders and treating different immune diseases.