|Detection of FCRL3/FcRH3 in Human Blood Lymphocytes by Flow Cytometry. Human peripheral blood lymphocytes were stained with Mouse Anti-Human NCAM‑1/CD56 PE‑conjugated Monoclonal Antibody (Catalog # FAB2408P) and either (A) Mouse Anti-Human FCRL3/FcRH3 APC‑conjugated Monoclonal Antibody (Catalog # FAB3126A) or (B) Mouse IgG1 Allophycocyanin Isotype Control (Catalog # IC002A). View our protocol for Staining Membrane-associated Proteins.|
FCRL3 (Fc Receptor-Like 3), also known as FcRH3, IRTA3, and SPAP2, is a 110 kDa molecule with sequence homology to classical Fc receptors. The type 1 transmembrane FCRL proteins contain from three to nine immunoglobulin-like domains. They are differentially expressed within the B cell lineage and can either promote or inhibit B cell proliferation and activation (1). Mature human FCRL3 consists of a 556 amino acid (aa) extracellular domain (ECD) with six Ig-like domains, a 21 aa transmembrane segment, and a 140 aa cytoplasmic domain with four immunotyrosine inhibitory motifs (ITIMs) (2-4). Within the ECD, human and mouse FCRL3 share 35% aa sequence identity. Alternate splicing generates several additional isoforms with deletions or substitutions in both the extracellular and intracellular regions. These include potentially secreted forms that are truncated following the second Ig-like domain (4). FCRL3 is expressed in secondary lymphoid organs on the surface of mature naïve and memory B cells, NK cells, and B cell lines derived from chronic lymphocytic leukemias (2, 3, 5). It is upregulated on B cells following LPS or anti-CD40 stimulation (6). A polymorphism in the FCRL3 promoter induces enhanced transcription and is associated with the development of autoimmune disorders in a Japanese population (6, 7). Tyrosine phosphorylation within the ITIMs of FCRL3 enables its association with SHP-1 (4).