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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

Genes & Immunity volume 8, pages 604–612 (2007)Cite this article

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.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, The Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA, USA

    Z S M Rahman & T Manser

  2. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA

    H Niu, D Perry & L Morel

  3. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    E Wakeland

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  1. Z S M Rahman
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  2. H Niu
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  3. D Perry
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  4. E Wakeland
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  5. T Manser
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  6. L Morel
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Correspondence to L Morel.

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Rahman, Z., Niu, H., Perry, D. et al. Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production. Genes Immun 8, 604–612 (2007). https://doi.org/10.1038/sj.gene.6364423

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  • DOI: https://doi.org/10.1038/sj.gene.6364423

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