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.
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.
复制标题
新诊断的胰岛素依赖性糖尿病患者中 B 细胞致力于产生胰岛素抗体的频率以及产生高亲和力的人单克隆胰岛素 IgG 的频率。
作者：
Paolo Casali;M. Nakamura;F. Ginsberg‐Fellner;A. Notkins
胰岛素依赖型糖尿病（I型）患者在临床发病时可检测到循环中的胰岛素自身抗体。为了描述IDDM患者自身抗体反应的特征，我们测定了12例新诊断的IDDM患者和9例健康受试者以及17例胰岛素治疗的IDDM患者中致力于产生胰岛素IgM、IgG和伊加的循环B细胞的频率。我们发现，在胰岛素治疗前，新诊断的IDDM患者的循环中，B细胞致力于产生抗胰岛素IgG，而不是IgM，自身抗体的频率要高得多（0.209 +/-0.142%，总IgG产生细胞前体的平均值+/- SD）与年龄匹配的健康对照（总IgG产生细胞前体的0.032 +/- 0.030%）相比。在接受胰岛素治疗的IDDM患者中，产生抗胰岛素IgG抗体的细胞占总IgG产生细胞前体的0.177 +/-0.139%。从IDDM患者的B细胞产生IgG mAb显示它们是单反应性的，即，它们与胰岛素结合，但不与所测试的其它Ag结合，并显示出对胰岛素的高亲和力（Kd约为10（-7）摩尔/升）。相反，来自健康受试者的IgG mAb是多反应性的，即，它们与所有测试的Ag结合，并显示出对胰岛素的低至中等亲和力（Kd约为10（-5）至10（-6）摩尔/升）。这些发现表明，淋巴细胞致力于生产高亲和力的IgG胰岛素自身抗体是常见的B细胞库在发病时的胰岛素依赖型糖尿病。
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 to insulin in 12 newly diagnosed IDDM patients and, for comparison, in 9 healthy subjects and 17 insulin-treated IDDM patients. We found that B cells committed to the production of anti-insulin IgG, but not 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 precursors). 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 (Kd approximately 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 (Kd approximately 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.