Update on Fc receptor-like (FCRL) family: new immunoregulatory players in health and diseases

Fc receptor-like (FCRL) molecules, as recently identified members of the immunoglobulin superfamily (IgSF), are preferentially expressed by B-cells. They have variable number of extracellular immunoglobulin-like domains and cytoplasmic activating ITAMs and/or inhibitory ITIMs. FCRL1-5 are dominantly expressed in different stages of B-cells development. But, FCRL6 is preferentially expressed in different subsets of T-cells and NK cells. FCRL1-5 could regulate different features of B-cell evolution such as development, differentiation, activation, antibody secretion and isotype switching. Areas covered: Improved understanding of FCRL expression may grant B-cells and finally its signaling pathways, alone or in cooperation with other signaling molecules, as interesting new targets for diagnostic, monitoring and immunotherapeutic modalities; although further investigations remain to be defined. Recent investigations on different family members of FCRL proteins have substantiated their differential expression on different tissues, malignancies, immune related disease and infectious diseases. Expert opinion: FCRLs restricted expressions in normal B-cells and T-cell subsets accompanied with their overexpression in B-cell malignancies introduce them as logical candidates for the development of antibody- and cell-based immunotherapy approaches in B-cell malignancies, immune-mediated and infectious diseases. FCRLs would be applied as attractive and specific targets for immunodiagnostic approaches, clinical prognosis as well as disease monitoring of relevant patients.