Frequency of B cells committed to the production of antibodies to insulin in newly diagnosed patients with insulin-dependent diabetes mellitus and generation of high affinity human monoclonal IgG to insulin

P. Casali, M. Nakamura, F. Ginsberg-Fellner, A. L. Notkins

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Abstract

Circulating autoantibodies to insulin can be detected in patients with insulin-dependent (type I) diabetes mellitus (IDDM) at the onset of the clinical disease. To characterize the autoantibody response in IDDM patients, we determined the frequency of circulating B cells committed to the production of IgM, IgG, and IgA insulin in 12 newly diagnosed IDDM patients and, for comparison, 9 healthy subjects and 17 insulin-treated IDDM patients. We found that B cells committed to the production of anti-insulin IgG, but no IgM, autoantibodies are present at much higher frequency in the circulation of newly diagnosed IDDM patients before insulin treatment (0.209 ± 0.142%, mean value ± SD of total IgG-producing cell precursors) as compared with age-matched healthy controls (0.032 ± 0.030% of total IgG-producing cell percursors). In IDDM patients who had been treated with insulin, cells producing IgG antibody to insulin were 0.177 ± 0.139% of total IgG-producing cell precursors. Generation of IgG mAb from B cells of IDDM patients revealed that they were monoreactive, i.e., they bound to insulin, but to none of the other Ag tested, and displayed a high affinity for insulin (K(d) ~ 10-7 moles/liter). In contrast, the IgG mAb derived from healthy subjects were polyreactive, i.e, they bound to all Ag tested, and displayed a low to moderate affinity for insulin (K(d) ~ 10-5 to 10-6 moles/liter). These findings show that lymphocytes committed to the production of high affinity IgG autoantibodies to insulin are common in the B cell repertoire at the onset of IDDM.

Original languageEnglish (US)
Pages (from-to)3741-3747
Number of pages7
JournalJournal of Immunology
Volume144
Issue number10
Publication statusPublished - Jan 1 1990

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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