Suppression of insulitis and diabetes in B cell-deficient mice treated with streptozocin: B cells are essential for the TCR clonotype spreading of islet-infiltrating T cells

Shiori Kondo, Isao Iwata, Keizo Anzai, Tomoyuki Akashi, Shigeharu Wakana, Kumiko Ohkubo, Hitoshi Katsuta, Junko Ono, Takeshi Watanabe, Yoshiyuki Niho, Seiho Nagafuchi

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10 Citations (Scopus)

Abstract

In order to clarify the role of B cells in the development of insulitis and diabetes, B cell-deficient (B-) mice treated with streptozocin (STZ) were studied. The extent of insulitis and the cumulative incidence of diabetes were significantly suppressed in B- mice (P<0.0001), indicating that B cells are crucial for the progression of insulitis and diabetes. Accumulation of both CD4+ T cells and B cells was observed in islets of B+ mice, while CD4+ T cells but not B cells were found in B- mice. A few CD8+ T cells and macrophages were detectable in both types of mice. The immunohistochemical study did not reveal any change in the subpopulations of infiltrating lymphocytes except for the absence of B cells in the B- mice. TCR Vβ gene repertoire usage of islet-infiltrating T cells was restricted to some extent in the B+ or B- mice, but there was no significant difference between the B+ and B- mice, suggesting that the initial islet-reactive T cell response can occur in the absence of B cells. In contrast, TCR clonotype spreading of islet-infiltrating T cells was significantly suppressed in B- mice compared with B+ mice (P<0.0001). These data suggest that initial priming of T cells is not impaired and TCR Vβ repertoire usage is not limited by the lack of B cells, while B cells are important essentially for the spreading of islet-infiltrating clonal T cells in autoimmune diabetic mice induced with STZ.

Original languageEnglish
Pages (from-to)1075-1083
Number of pages9
JournalInternational immunology
Volume12
Issue number7
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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