Immunogenetics

, Volume 51, Issue 6, pp 429–435

Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility

Authors

  • Y. Jiang
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Sachiko Hirose
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Masaaki Abe
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Reiko Sanokawa-Akakura
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Mareki Ohtsuji
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Xiaoyi Mi
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • N. Li
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Y. Xiu
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Danqing Zhang
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • J. Shirai
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Yoshitomo Hamano
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • Hiroaki Fujii
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
  • T. Shirai
    • Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: toshirai@med.juntendo.ac.jp Tel.: +81-3-58021038 Fax: +81-3-38133164
ORIGINAL PAPER

DOI: 10.1007/s002510050641

Cite this article as:
Jiang, Y., Hirose, S., Abe, M. et al. Immunogenetics (2000) 51: 429. doi:10.1007/s002510050641

Abstract

 Autoimmune diseases involve multiple genes. While functions of these genes are largely unknown, some may be related to an intrinsic hyperresponsiveness of B cells. B-cell responses are controlled by signaling thresholds through the B-cell antigen receptor (BCR) complex. The B1 isoform of type II IgG Fc receptors (FcγRIIB1) is exclusively expressed on B cells and serves as a negative regulator for inhibiting BCR-elicited activation. Thus, its allelic variants associated with functional deficits could be examined for possible associations with susceptibility to autoimmune diseases. We found that there are three types of polymorphisms in the reported FcγRIIB transcription regulatory regions in mouse strains. Compared to normal healthy mouse strains (group III), autoimmune disease-prone strains (group I) share three deletion sites: two in the promoter region and one in the third intron. Strains (group II) that per se are not autoimmune-prone, but have potentials to accelerate autoimmune diseases share two deletion sites in the third intron: one identical to that in group I and the other unique to group II. These polymorphisms correlated well with extents of down-regulation of FcγRIIB1 expression in germinal-center B cells upon stimulation with antigens and up-regulation of IgG antibody responses. Our data imply that these FcγRIIB polymorphisms are selected evolutionarily for natural defense against pathogens, and that such polymorphisms may, in turn, form the basis of one aspect of autoimmune susceptibility.

Key words PolymorphismFcγRIIB1Systemic lupus erythematosusGerminal-center B cellsHyper-IgG

Copyright information

© Springer-Verlag Berlin Heidelberg 2000