Disease relevance of FCRLA

• FREB is also expressed in some B cell lymphomas, most of which have centroblast origin [1].
• These results suggest that FCRL/FREB may function in melanocytes and melanoma and may be useful for development of diagnostic methods for various pigment disorders and immunotherapy of melanoma [2].
• Our results also showed that FCRL tended to be negative in T-cell-rich B-cell lymphoma and in classical Hodgkin's disease [3].

High impact information on FCRLA

• The observation that FCRL representatives are members of an ancient multigene family that share a common ancestor with the classical FCR is underscored by their linked genomic locations, gene structure, shared extracellular domain composition, and utilization of common cytoplasmic tyrosine-based signaling elements [4].
• Here we identify a SNP in the promoter region of FCRL3, a member of the Fc receptor-like family, that is associated with susceptibility to rheumatoid arthritis (odds ratio = 2.15, P = 0.00000085) [5].
• By using specific monoclonal antibodies, we show that FREB is preferentially expressed in germinal center centroblasts, which undergo affinity maturation and class-switch recombination [1].
• Here, we report the identification of Fc receptor homolog expressed in B cells (FREB), a unique B cell-specific molecule that is distantly related to FcgammaRI (receptor I for the Fc fragment of IgG) and is encoded on human chromosome 1q, within the FcgammaR gene region [1].
• Novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients [2].

Biological context of FCRLA

• In a database search for additional relatives of this family we identified expressed sequence tag representatives of a new FcR-related molecule (hFcRX) and its mouse ortholog (mFcRX) [6].

Anatomical context of FCRLA

• Together, these characteristics indicate that FREB may have a unique role in B cell differentiation [1].
• In COS-7 cells transiently transfected with two human FCRL isoforms, both resided intracellularly [7].
• Spleen and tonsils were found to be the major sources of FCRL mRNA in human tissues [7].
• 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 [7].
• FcRX transcripts are found primarily in secondary lymphoid tissues, where they are expressed by B lineage cells [6].

Analytical, diagnostic and therapeutic context of FCRLA

• Western blotting of tonsil cell lysate using FCRL-specific antibodies recognized a 44-kDa protein produced as a monomer containing free sulfhydryl groups [7].
• One of the remaining 3 genes, FCRL/FREB, encoding a member of the Fc receptor family that was previously reported to express in germinal center B cells, was found to express preferentially in melanocytes and melanoma tissues by RT-PCR and Northern blot analysis [2].

References