Baxendale H E, Johnson M, Stephens R C M, Yuste J, Klein N, Brown J S, Goldblatt D
Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, London, UK.
Clin Exp Immunol. 2008 Jan;151(1):51-60. doi: 10.1111/j.1365-2249.2007.03535.x. Epub 2007 Nov 5.
The molecular and functional characteristics of natural antibody from the preimmune repertoire have not been explored in detail in man. We describe seven human IgM monoclonal antibodies selected on the basis of pneumococcal polysaccharide binding that share both molecular and functional characteristics with natural antibody, suggesting a common B cell lineage origin. Unlike class-switched antibodies, which are serotype-specific, the antibodies were polyreactive and bound all pneumococcal polysaccharide capsular serotypes tested. Some bound endogenous antigens, including blood group antigens and intermediate filament proteins. All the antibodies used unmutated heavy chain V (IGHV) that are expressed at an increased frequency in the elderly and in the preimmune repertoire. The CDR3 was characterized by long length (mean aa 18.4 (+/-4.2) and selective use of IGHD6 (P < 0.001) and IGHJ6 (P < 0.01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo.
在人类中，尚未对免疫前库中天然抗体的分子和功能特性进行详细研究。我们描述了七种基于肺炎球菌多糖结合而筛选出的人IgM单克隆抗体，它们与天然抗体具有共同的分子和功能特性，提示其起源于共同的B细胞谱系。与血清型特异性的类别转换抗体不同，这些抗体具有多反应性，能结合所有测试的肺炎球菌多糖荚膜血清型。一些抗体还能结合内源性抗原，包括血型抗原和中间丝蛋白。所有抗体均使用未发生突变的重链V（IGHV），这些基因在老年人和免疫前库中的表达频率增加。其互补决定区3（CDR3）的特点是长度较长（平均氨基酸长度为18.4（±4.2）），且选择性使用IGHD6（P < 0.001）和IGHJ6（P < 0.01）家族基因。表达IGHV1 - 69和IGHV 3 - 21的克隆在体内对侵袭性肺炎球菌疾病提供了显著的被动保护作用。
