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

Wilson, T.; Colonna, Marco

doi:10.1038/sj.gene.6364185

Cited by 19 publications

(26 citation statements)

References 21 publications

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“…Surface IgM expression on both CD138 þ B220 þ plasmablasts and CD138 þ B220 À/lo PC was significantly lower in B6.Sle1(111-148) than in either B6 or B6.Sle1a(15-353) mice (data not shown). Consistent with the surface expression, the percentage of intracellular IgM þ was also significantly lower in both 16 and Fcrlb (FcRY or Freb1) 17 that are contained in the B6.Sle1(111-148) interval, and potentially not in the B6.Sle1a(15-353) interval since they are situated in the region of recombination between the D1MIT270 and D1MIT147 markers. These two FcR family members are differentially expressed on B cells, including GC B cells, but their function is yet unknown.…”

Section: Resultssupporting

confidence: 65%

“…These two FcR family members are differentially expressed on B cells, including GC B cells, but their function is yet unknown. 18,19 Interestingly, FCRL3, a member of this family in humans, is associated with RA and other autoimmune conditions, including lupus. 20 We are currently investigating whether one or both of these genes present allelic differences between NZW and B6.…”

Section: Resultsmentioning

confidence: 99%

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Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production

et al. 2007

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The inhibitory receptor FcgRIIb regulates B-cell functions. Genetic studies have associated Fcgr2b polymorphisms and lupus susceptibility in both humans and murine models, in which B cells express reduced FcgRIIb levels. Furthermore, FcgRIIb absence results in lupus on the appropriate genetic background, and lentiviral-mediated FcgRIIb overexpression prevents disease in the NZM2410 lupus mouse. The NZM2410/NZW allele Fcgr2b is, however, located in-between Sle1a and Sle1b, two potent susceptibility loci, making it difficult to evaluate Fcr2b NZW independent contribution. By using two congenic strains that each carries only Sle1a (B6.Sle1a(15-353)), or Fcr2b NZW in the absence of Sle1a or Sle1b (B6.Sle1(111-148)), we show that the Fcr2b NZW allele does not upregulate its expression on germinal center B cells and plasma cells, as does the C57BL/6 allele on B6.Sle1a(15-353) B cells. Furthermore, in the absence of the flanking Sle1a and Sle1b, Fcr2b NZW does not produce an autoimmune phenotype, but is associated with an increased number of class-switched plasma cells. These results show that while a lower level of FcgRIIb does not by itself induce the development of autoreactive B cells, it has the potential to amplify the contribution of autoreactive B cells induced by other lupus-susceptibility loci by enhancing the production of class-switched plasma cells.

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Section: Resultssupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production

et al. 2007

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“…FcRL1-6 are type I transmembrane proteins of the Ig superfamily, and all have one or more canonical ITAMs or ITIMs in their cytoplasmic tails. The ability to recruit tyrosine kinases or protein tyrosine phosphatases has been reported for all of these receptors (8)(9)(10)(11)(12)(13)(14)(15), with bona fide activating potential found for FcRL1 (12) and potent inhibitory potential found for FcRL4 and FcRL5 (10,11). This potential to regulate B cell responses appears to be conserved in mouse FcR homolog 3/FcRL5 (16).…”

Section: F Crs Bindmentioning

confidence: 98%

“…Whereas FcRLB has Ig-like domains with homology to all three domains of FcgRI, FcRLA contains Ig-like domains homologous to only the second and third domains of FcgR1, preceded by an N-terminal domain rich in acidic residues as well as potentially unpaired cysteines. In addition, FcRLB seems to be expressed in only a tiny fraction of nondividing B cells, whereas FcRLA is expressed at low levels in mantle zone B cells and at higher levels within germinal centers and splenic marginal zone B cells in humans (13,(22)(23)(24)(25)(26)(27).…”

Section: F Crs Bindmentioning

confidence: 99%

Fc Receptor-Like A Associates with Intracellular IgG and IgM but Is Dispensable for Antigen-Specific Immune Responses

Wilson

Gilfillan

Colonna

2010

The Journal of Immunology

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FcR-like (FcRL) proteins comprise a family of lymphocyte receptors with homology to FcγRI. Among these receptors, FcRLA is uniquely interesting due to its intracellular localization, unusual structural features, and high expression within human germinal center and marginal zone B cells. Our analysis of human cell lines has confirmed that this receptor is not secreted but is maintained as an intracellular protein in B cells where it interacts with Igs, consistent with a possible role in Ab assembly. By generating FcRLA-specific antisera as well as knockout mice, we were able to unequivocally demonstrate that FcRLA protein is expressed exclusively in all mouse B cells. We also found that FcRLA is not required for the generation of Ag-specific humoral immune responses to T-dependent or T-independent Ags. However, given its highly conserved structure and universal expression within B cells, it is probable that FcRLA functions similarly in humans and mice. Cumulatively, our data suggest that FcRLA plays a role in Ig assembly that can be compensated for by other proteins.

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“…Fc receptor-like (FCRL) molecules are a family of Fc receptor homologs comprising eight structurally related members [7][8][9][10] [18][19][20]. Recent studies indicate that the activated level of B cells in human peripheral blood lymphocytes with HBV infection is higher than that of normal controls [21].…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

The expression profile of Fc Receptor-like Y in B lymphocytes with hepatitis B virus induced diseases

Wang¹,

Yang²,

Hao³

et al. 2011

Folia Histochem Cytobiol.

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Abstract:Abstract: Abstract: Abstract: Abstract: The Fc Receptor-like Y (FcRY) molecule is preferentially expressed by B lymphocytes and has recently been considered as a potential therapeutic target for B cell malignancies. In this study, we investigated the correlation between FcRY expression profile, B lymphocytes population and different HBV infection disease status. The FcRY expression level on B lymphocytes and the number of B lymphocytes population from peripheral blood in 27 healthy controls (HC) and 65 patients with HBV-induced diseases, including chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), were analyzed using quantitative real-time PCR and flow cytometry. The results showed the level of FcRY expression and frequency of germinal center (GC) B lymphocytes from peripheral blood were significantly correlated with the HBV-related disease status, which was highest in HCC and LC patients, lowest in healthy donors, and in the middle in patients with CHB. Our study indicates that there is a significant correlation between FcRY expression profile, B lymphocytes population and HBV-induced diseases. However, the roles of FcRY and B lymphocytes in HBV-induced diseases are unclear and need further investigation.

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

Cited by 19 publications

References 21 publications

Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production

Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production

Fc Receptor-Like A Associates with Intracellular IgG and IgM but Is Dispensable for Antigen-Specific Immune Responses

The expression profile of Fc Receptor-like Y in B lymphocytes with hepatitis B virus induced diseases

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