Fc Receptor-Like Proteins in Pathophysiology of B-cell Disorder.

Mollie Capone,John Matthew

doi:10.4172/2155-9899.1000427

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.

Highlights

Many different biological functions including antibody secretion, antigen (Ag) presentation, and proliferation of other immune cells are regulated by B-lymphocytes
Studies were done in which non-functional FCRL2–FCRL5 ITIMs were transfected into a B-cell line and this caused an increase in calcium influx compared with the BCR engagement on its own [52], suggesting that Fc receptor-like (FCRL) may regulate both humoral and cell mediated immune responses
This study suggests that FCRL6 may influence HIV infection, and further studies may find ways to be able to utilize it in diagnosis or treatment of HIV infection

Summary

Introduction

Many different biological functions including antibody secretion, antigen (Ag) presentation, and proliferation of other immune cells are regulated by B-lymphocytes. The preferential expression of FCRL proteins on B-lymphocytes, and the presence of ITAMlike and ITIM structural elements in their intracellular domains, suggests that they play a role in the regulation of B-lymphocyte activation. The same group identified two additional homologs that had no obvious transmembrane sequences, which they named FCRL1 and FCRL2 [35,42]; these proteins were later renamed FCRLA and FCRLB, respectively [22,37].

Results

Conclusion