|Detection of FCRL5/FCRL3 in Human CD19+ Lymphocytes by Flow Cytometry. Human blood‑derived CD19+ lymphocytes were stained with Mouse Anti-Human FCRL5/FCRL3 Monoclonal Antibody (Catalog # MAB20871, filled histogram) or isotype control antibody (Catalog # MAB0041, open histogram), followed by Allophycocyanin-conjugated Anti-Mouse IgG F(ab')2 Secondary Antibody (Catalog # F0101B).|
Fc Receptor-Like 5 (FCRL5), also known as FcRH5, IRTA2, and CD307, is a 120 kDa protein 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, 2). According to R&D Systems testing, FCRL5 binds to purified human IgG with high affinity. Mature human FCRL5 consists of a 836 amino acid (aa) extracellular domain (ECD) with nine Ig-like domains, a 21 aa transmembrane segment, and a 105 aa cytoplasmic domain with one immunotyrosine activation motif (ITAM) and two immunotyrosine inhibitory motifs (ITIMs) (1, 3). Mouse FCRL5 contains only five Ig-like domains in its ECD. It shares 49% aa sequence identity with human FCRL5 within common regions. Alternate splicing of human FCRL5 generates isoforms that consist of approximately the first one, six, or eight Ig-like domains (3, 4). FCRL5 expression is restricted to mature B lineage cells in lymphoid tissues and blood (3, 5‑7). Its ligation inhibits signaling through the B cell antigen receptor (8). Epstein-Barr virus transformation of B cells induces the up‑regulation of surface FCRL5 by a direct effect of its EBNA2 protein on FCRL5 gene transcription (9). The FCRL5 gene maps to the 1q21 chromosomal locus, a common site of rearrangements in B cell malignancies, and the FCRL5 protein is preferentially expressed in cell lines with 1q21 abnormalities (3). FCRL5 is up‑regulated on tumor cells in some types of B cell malignancies (6, 10‑12). In addition, soluble FCRL5 is elevated in the serum of many B cell leukemia patients (11, 13).
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