Fc Receptor Homolog 3 Is a Novel Immunoregulatory Marker of Marginal Zone and B1 B Cells

Abstract

Two members of the recently identified FcR homolog (FcRH) family in mice demonstrate preferential B cell expression. One of these, FcRH3, encodes a type I transmembrane protein with five extracellular Ig domains and a cytoplasmic tail with a consensus ITIM and a noncanonical ITAM. Analysis of full-length cDNAs from five different mouse strains defines two FcRH3 alleles. A panel of FcRH3-specific mAbs was generated to define its expression pattern and functional potential on B lineage cells. Although poorly detected on the majority of bone marrow or peripheral blood cells, FcRH3 was readily identified on splenic marginal zone (MZ) and MZ precursor B cells, but not on the bulk of newly formed B cells, follicular B cells, germinal center B cells, and plasma cells. In the peritoneal cavity, FcRH3 was found on B1 cells, and not on the majority of B2 cells. Consistent with its possession of an ITIM and ITAM-like sequence, FcRH3 was tyrosine phosphorylated following pervanadate treatment, and its coligation with the BCR inhibited calcium mobilization. These results suggest FcRH3 is a novel immunoregulatory marker of MZ and B1 B lineage cells.

FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia

“…Although only 2 of the 5 human FCRL representatives are evident in mice (FCRL1 and FCRL5), FCRL5, which has similar features to human FCRL3 and FCRL5, is distinctly expressed by MZ and B1 B cells. 62 These data suggest that the expression patterns of FCRL representatives may also be useful for future studies designed at further defining the normal CLL counterpart.…”

CD36 Is Differentially Expressed on B Cell Subsets during Development and in Responses to Antigen

“…The differential expression of CD36 by B cell subsets provides another useful marker for discrimination of MZ B cells along with CD9 and FCRL5 (8,9). However, because CD36 is rapidly induced in FO B cells by stimulation by TLR ligands and ␣-CD40, it may represent an early activation marker of B cells, similar to CD25 and CD69.…”

“…Spleen cells at day 7 after SRBC injection were stained. Germinal center cells were defined, as previously described (9,46 …”

“…Previously, our laboratory identified two surface markers, CD9 and FCRL5 (Fc receptor-like 5), which help distinguish MZ B and B1 cells from FO B cells in mice (8,9). Recently, we and others showed by different approaches that CD36 is expressed on resting MZ B cells, but not the majority of FO B cells (10,11).…”

FCRL5 exerts binary and compartment-specific influence on innate-like B-cell receptor signaling

“…In contrast, FCRL2-5, which feature one or more consensus immunoreceptor tyrosinebased inhibition motifs (ITIM) as well as ITAM-like sequences, all inhibit BCR activation via recruitment of the SH2 domain-containing SHP-1 and/or SHP-2 phosphatases (27)(28)(29)(30). We have shown previously that the FCRL5 mouse ortholog discretely marks innate-like B cells and possesses an ITIM as well as an ITAM-like sequence that differs from the canonical motif (D/EX 2-3 YXXL/ IX 6-8 YXXL/I), with a glutamic acid residue rather than an aliphatic residue at the second Y+3 position (31). Although FCRL5 inhibits BCR-mediated calcium mobilization in MZ B cells, the molecular basis for this activity and its function in B1 B cells remains unclear.…”