Fc receptor-like 2 (FCRL2), also known as FcRH2 and IRTA4, belongs to the family of glycoprotein homologs of classical immunoglobulin (Ig) Fc receptors. In human, the type I transmembrane FCRL protein family contains from three to nine immunoglobulin-like domains (1, 2). Mature human FcRH2 consists of a 382 amino acid (aa) extracellular domain (ECD) with four Ig-like C2-set domains, a 21 aa transmembrane segment, and an 86 aa cytoplasmic domain with one ITAM-like, and two ITIM-like motifs (3‑5). Alternate splicing of human FCRL2 may generate isoforms with N-terminal, internal, or C-terminal deletions (4, 5). The gene for FcRH2 maps to the human Iq21-23 locus which is a hotspot for chromosomal translocation events associated with B cell malignancies (3, 6). Although there are several Fc receptor-like genes in the mouse, none of these is a clear ortholog to human FCRL2 (7). FCRL proteins are differentially expressed among B cells (2). FCRL2 is preferentially expressed on naïve and CD27+ memory B cells within the spleen, lymph nodes, tonsils, and peripheral blood (3, 4, 8, 9). It is also expressed on most B cells in B cell chronic lymphocytic leukemia (B-CLL) patients (10). FCRL2 upregulation is associated with mutation of the immunoglobulin heavy chain variable (IGHV) and less aggressive forms of B-CLL (9, 11).
