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

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 (FcgammaRIIB1) 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 FcgammaRIIB 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 FcgammaRIIB1 expression in germinal-center B cells upon stimulation with antigens and up-regulation of IgG antibody responses. Our data imply that these FcgammaRIIB 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.
AuthorsY Jiang, S Hirose, M Abe, R Sanokawa-Akakura, M Ohtsuji, X Mi, N Li, Y Xiu, D Zhang, J Shirai, Y Hamano, H Fujii, T Shirai
JournalImmunogenetics (Immunogenetics) Vol. 51 Issue 6 Pg. 429-35 (May 2000) ISSN: 0093-7711 [Print] United States
PMID10866109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Autoantibodies
  • Fc gamma receptor IIB
  • Immunoglobulin G
  • Receptors, IgG
Topics
  • Animals
  • Antigens, CD (biosynthesis, genetics)
  • Autoantibodies (biosynthesis)
  • B-Lymphocytes (immunology, metabolism)
  • Base Sequence
  • Female
  • Genetic Predisposition to Disease (genetics)
  • Germinal Center (cytology, immunology, metabolism)
  • Immunoglobulin G (biosynthesis)
  • Lupus Erythematosus, Systemic (genetics, immunology)
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred MRL lpr
  • Mice, Inbred NOD
  • Mice, Inbred NZB
  • Molecular Sequence Data
  • Polymorphism, Genetic (genetics)
  • Receptors, IgG (biosynthesis, genetics)
  • Regulatory Sequences, Nucleic Acid (genetics, immunology)

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