FCRL, a novel member of the leukocyte Fc receptor family possesses unique structural features

Abstract

A novel conserved member of the leukocyte Fc receptor (FcR) family was identified in human and mouse. The presumably secreted protein, designated FCRL (FcR‐like) is comprised of four domains. The three N‐terminal domains are related to the extracellular region of FcγRI, with the second (35–37% residue identity) and the third (46–52%) domains showing highest similarity. The C‐terminaldomain is a unique sequence enriched with proline residues. In humans, alternative transcripts for six FCRL isoforms were revealed. Spleen and tonsils were found to be the major sources of FCRL mRNA in human tissues. Western blotting of tonsil cell lysate using FCRL‐specific antibodies recognized a 44‐kDa protein produced as a monomer containing free sulfhydryl groups. The monomer, however, was able to form disulfide‐linked homo‐oligomer upon oxidation. In COS‐7 cells transiently transfected with two human FCRL isoforms, both resided intracellularly. Immunohistochemical staining of tonsil sections demonstrated the FCRL expression in germinal centers, suggesting that the protein may be implicated in germinal center‐specific stages of B cell development. The phylogenetic analysis of the FCRL relationships with the leukocyte FcR supports a view that the three‐domain structure was primordial in the evolution of the family.

Genomic organization of classical human low-affinity Fcγ receptor genes

“…Both genes contain potential STAT The organization of the low-affinity Fc␥R genes at chromosome 1q23. The assembly order and the orientation with regard to the centromere and telomere of the Fc␥R cluster genes and the nearby genes FcRL, 46,47 DUSP12 and ATF6 are shown. Duplication and deletion of Fc␥RIIIB have been described.…”

A new Fc receptor homolog, FREB2, found in germinal center B cells

“…Based on sequence features and genomic position, the gene encoding FREB2 is likely to be the gene predicted to exist and given the names FcRY 3 or FCRL2. 16 The cDNA and amino-acid sequences of human and mouse FREB2 are listed in Genbank under accession numbers AY786314 and AY513660.…”

“…19 The existence of genes encoding other Fc receptor homologs in addition to these has been predicted. 3,16 In this study, we have identified a new Fc receptor homolog, FREB2, with immunoglobulin domains homologous to FcgRI, and a C-terminal domain previously thought to be unique to FREB1. Its expression within nonproliferating cells of the germinal center suggests a unique role for this protein in regulating B-cell differentiation.…”

“…These unique attributes suggested a novel role for FREB1 in the development of B-cell responses. [15][16][17][18] Like other Fc receptor homologs, expression of FREB1 within B-cell neoplasms is widespread, with particularly high abundance in small lymphocytic, follicular, marginal zone, lymphoplasmacytic, and diffuse large B-cell lymphomas, as well as lymphocyte-predominant Hodgkin's disease. 15,18 The abundance of FREB1 within B-cell tumors is suggestive that it may be beneficial diagnostic or prognostic indicators for treating lymphoma.…”

Novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients

“…After purification, the recombinant protein was suspended in sample buffer (0.1 M Tris-HCl, pH 6.8, 4% SDS, 20% glycerol, 1 M 2-mercaptoethanol). SDS-PAGE was carried out as described previously 28 and the separated proteins were blotted onto nitrocellulose membranes. The membranes were incubated with TBST-SM (137 mM NaCl, 2.68 mM KCl, 25 mM Tris-HCl, 0.02% Tween-20 containing 5% nonfat milk) at 4°C overnight.…”