Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

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


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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others


  1. Wakeland EK, Liu K, Graham RR, Behrens TW . Delineating the genetic basis of systemic lupus erythematosus. Immunity 2001; 15: 397–408.

    Article  CAS  Google Scholar 

  2. Ravetch JV, Bolland S . IgG Fc receptors. Ann Rev Immunol 2001; 19: 275–290.

    Article  CAS  Google Scholar 

  3. Naoyuki T, Zen-ichiro H, Katsushi T . Role of B cell inhibitory receptor polymorphisms in systemic lupus erythematosus: a negative times a negative makes a positive. J Hum Genet 2006; 51: 741–750.

    Article  Google Scholar 

  4. Mackay M, Stanevsky A, Wang T, Aranow C, Li M, Koenig S et al. Selective dysregulation of the Fc{gamma}IIB receptor on memory B cells in SLE. J Exp Med 2006; 203: 2157–2164.

    Article  CAS  Google Scholar 

  5. Su K, Yang H, Li X, Li X, Gibson AW, Cafardi JM et al. Expression profile of FcγRIIb on leukocytes and its dysregulation in systemic lupus erythematosus. J Immunol 2007; 178: 3272–3280.

    Article  CAS  Google Scholar 

  6. Bolland S, Ravetch JV . Spontaneous autoimmune disease in FcγRIIb-deficient mice results from strain-specific epistasis. Immunity 2000; 13: 277–285.

    Article  CAS  Google Scholar 

  7. Fukuyama H, Nimmerjahn F, Ravetch JV . The inhibitory Fc receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells. Nat Immunol 2005; 6: 99–106.

    Article  CAS  Google Scholar 

  8. Jiang Y, Hirose S, Sanokawa-Akakura R, Abe M, Mi X, Li N et al. Genetically determined aberrant down-regulation of FcγRIIb1 in germinal center B cells associated with hyper-IgG and IgG autoantibodies in murine systemic lupus erythematosus. Int Immunol 1999; 11: 1685–1691.

    Article  CAS  Google Scholar 

  9. Pritchard NR, Cutler AJ, Uribe S, Chadban SJ, Morley BJ, Smith KGC . Autoimmune-prone mice share a promoter haplotype associated with reduced expression and function of the Fc receptor FcgRII. Curr Biol 2000; 10: 227–230.

    Article  CAS  Google Scholar 

  10. Rahman ZSM, Manser T . Failed up-regulation of the inhibitory IgG Fc receptor FcγRIIb on germinal center B cells in autoimmune-prone mice is not associated with deletion polymorphisms in the promoter region of the FcγRIIb gene. J Immunol 2005; 175: 1440–1449.

    Article  CAS  Google Scholar 

  11. Mcgaha TL, Sorrentino B, Ravetch JV . Restoration of tolerance in lupus by targeted inhibitory receptor expression. Science 2005; 307: 590–593.

    Article  CAS  Google Scholar 

  12. Morel L, Yu Y, Blenman KR, Caldwell RA, Wakeland EK . Production of congenic mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain. Mamm Genome 1996; 7: 335–339.

    Article  CAS  Google Scholar 

  13. Morel L, Blenman KR, Croker BP, Wakeland EK . The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes. Proc Natl Acad Sci USA 2001; 98: 1787–1792.

    Article  CAS  Google Scholar 

  14. Chen Y, Cuda C, Morel L . Genetic determination of T cell help in loss of tolerance to nuclear antigens. J Immunol 2005; 174: 7692–7702.

    Article  CAS  Google Scholar 

  15. Rahman ZSM, Alabyev B, Manser T . FcγRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity. J Immunol 2007; 178: 897–907.

    Article  CAS  Google Scholar 

  16. Wilson TJ, Colonna M . A new Fc receptor homolog, FREB2, found in germinal center B cells. Genes Immun 2005; 6: 341–346.

    Article  CAS  Google Scholar 

  17. Masuda K, Davis RS, Maruyama T, Zhang J, He T, Cooper MD et al. FcRY, an Fc receptor related gene differentially expressed during B lymphocyte development and activation. Gene 2005; 363: 32–40.

    Article  CAS  Google Scholar 

  18. Davis RS, Wang YH, Kubagawa H, Cooper MD . Identification of a family of Fc receptor homologs with preferential B cell expression. Proc Natl Acad Sci USA 2001; 98: 9772–9777.

    Article  CAS  Google Scholar 

  19. Wilson TJ, Colonna M . A new Fc receptor homolog, FREB2, found in germinal center B cells. Genes Immun 2005; 6: 341–346.

    Article  CAS  Google Scholar 

  20. Kochi Y, Yamada R, Suzuki A, Harley JB, Shirasawa S, Sawada T et al. A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat Genet 2005; 37: 478–485.

    Article  CAS  Google Scholar 

  21. Xiang Z, Cutler AJ, Brownlie RJ, Fairfax K, Lawlor KE, Severinson E et al. FcγRIIb controls bone marrow plasma cell persistence and apoptosis. Nat Immunol 2007; 8: 419–429.

    Article  CAS  Google Scholar 

  22. William J, Euler C, Christensen S, Shlomchik MJ . Evolution of autoantibody responses via somatic hypermutation outside of germinal centers. Science 2002; 297: 2066–2070.

    Article  CAS  Google Scholar 

  23. Croker BP, Gilkeson G, Morel L . Genetic interactions between susceptibility loci reveal epistatic pathogenic networks in murine lupus. Genes Immun 2003; 4: 575–585.

    Article  CAS  Google Scholar 

  24. Erickson LD, Lin LL, Duan B, Morel L, Noelle RJ . A genetic lesion that arrests plasma cell homing to the bone marrow. Proc Natl Acad Sci USA 2003; 100: 12905–12910.

    Article  CAS  Google Scholar 

  25. Vora KA, Ravetch JV, Manser T . Amplified follicular immune complex deposition in mice lacking the Fc receptor gamma-chain does not alter maturation of the B cell response. J Immunol 1997; 159: 2116–2124.

    CAS  PubMed  Google Scholar 

  26. Rahman ZSM, Rao SP, Kalled SL, Manser T . Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling deficient mice. J Exp Med 2003; 198: 1157–1169.

    Article  CAS  Google Scholar 

  27. Morel L, Mohan C, Yu Y, Croker BP, Tian N, Deng A et al. Functional dissection of systemic lupus erythematosus using congenic mouse strains. J Immunol 1997; 158: 6019–6028.

    CAS  PubMed  Google Scholar 

  28. Mohan C, Alas E, Morel L, Yang P, Wakeland EK . Genetic dissection of SLE pathogenesis—Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes. J Clin Invest 1998; 101: 1362–1372.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to L Morel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


This article is cited by


Quick links