Somatic mutation in autoantibody-associated V(H) genes of circulating IgM+IgD+ B cells

Yasuhiko Munakata, Shin Ichiro Saito, Atsushi Hoshino, Tai Muryoi, Yasuhiko Hirabayashi, Shinobu Shibata, Toshihiko Miura, Tomonori Ishii, Tadao Funato, Takeshi Sasaki

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10 Citations (Scopus)

Abstract

Naive B cells expressing IgM and IgD on their surface have no or little somatic mutations in V genes. We have demonstrated that the human IgM+IgD+B cell clone (0-81), which expresses nephritogenic idiotypes, produces IgM anti-DNA antibodies which show monospecificity to DNA. Using a DNA probe which specifically links to the V(H) gene of antibody 0-81, we identified the counterpart germ-line V gene of 0-81, V3-7, which appears to be used by pathogenic autoantibodies in humans. Clone 0-81, which may belong to naive B cells in terms of cell phenotype, uses a somatically mutated V3-7 gene. We further studied DNA sequences of V3-7 genes in circulating IgM+IgD+B cells from normal subjects and patients with systemic lupus erythematosus (SLE). The results revealed that rearranged V3-7 genes in IgM+IgD+B cells from patients with SLE contained somatically mutated sequences at significantly increased frequencies. These data indicate an abnormal maturation of B cells in autoimmune states that may be associated with an escape of self-reactive B cells from the elimination process in the germinal center.

Original languageEnglish
Pages (from-to)1435-1444
Number of pages10
JournalEuropean Journal of Immunology
Volume28
Issue number5
DOIs
Publication statusPublished - 1998 May 1

Keywords

  • Anti-DNA antibody
  • IgD
  • V gene

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Munakata, Y., Saito, S. I., Hoshino, A., Muryoi, T., Hirabayashi, Y., Shibata, S., Miura, T., Ishii, T., Funato, T., & Sasaki, T. (1998). Somatic mutation in autoantibody-associated V(H) genes of circulating IgM+IgD+ B cells. European Journal of Immunology, 28(5), 1435-1444. https://doi.org/10.1002/(SICI)1521-4141(199805)28:05<1435::AID-IMMU1435>3.0.CO;2-R