Abstract
The inhibitory receptor FcγRIIb 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 FcγRIIb levels. Furthermore, FcγRIIb absence results in lupus on the appropriate genetic background, and lentiviral-mediated FcγRIIb 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 Fcr2bNZW independent contribution. By using two congenic strains that each carries only Sle1a (B6.Sle1a(15-353)), or Fcr2bNZW in the absence of Sle1a or Sle1b (B6.Sle1(111-148)), we show that the Fcr2bNZW 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, Fcr2bNZW 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 FcγRIIb 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 604-612 |
| Number of pages | 9 |
| Journal | Genes and Immunity |
| Volume | 8 |
| Issue number | 7 |
| DOIs | |
| State | Published - Oct 1 2007 |
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All Science Journal Classification (ASJC) codes
- Immunology
- Genetics
- Genetics(clinical)
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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. / Rahman, Z. S.M.; Niu, H.; Perry, D.; Wakeland, E.; Manser, T.; Morel, L.
In: Genes and Immunity, Vol. 8, No. 7, 01.10.2007, p. 604-612.Research output: Contribution to journal › Article
TY - JOUR
T1 - Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production
AU - Rahman, Z. S.M.
AU - Niu, H.
AU - Perry, D.
AU - Wakeland, E.
AU - Manser, T.
AU - Morel, L.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - The inhibitory receptor FcγRIIb 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 FcγRIIb levels. Furthermore, FcγRIIb absence results in lupus on the appropriate genetic background, and lentiviral-mediated FcγRIIb 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 Fcr2bNZW independent contribution. By using two congenic strains that each carries only Sle1a (B6.Sle1a(15-353)), or Fcr2bNZW in the absence of Sle1a or Sle1b (B6.Sle1(111-148)), we show that the Fcr2bNZW 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, Fcr2bNZW 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 FcγRIIb 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.
AB - The inhibitory receptor FcγRIIb 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 FcγRIIb levels. Furthermore, FcγRIIb absence results in lupus on the appropriate genetic background, and lentiviral-mediated FcγRIIb 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 Fcr2bNZW independent contribution. By using two congenic strains that each carries only Sle1a (B6.Sle1a(15-353)), or Fcr2bNZW in the absence of Sle1a or Sle1b (B6.Sle1(111-148)), we show that the Fcr2bNZW 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, Fcr2bNZW 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 FcγRIIb 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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U2 - 10.1038/sj.gene.6364423
DO - 10.1038/sj.gene.6364423
M3 - Article
C2 - 17713556
AN - SCOPUS:35548937869
VL - 8
SP - 604
EP - 612
JO - Genes and Immunity
JF - Genes and Immunity
SN - 1466-4879
IS - 7
ER -