Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease
Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease
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DOI：
10.1111/j.1365-2249.2007.03535.x
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发表时间：
2008-01-01
影响因子：
4.6
通讯作者：
Goldblatt, D.
中科院分区：
文献类型：
--
作者：
Baxendale, H. E.;Johnson, M.;Goldblatt, D.
天然抗体的分子和功能特性的preimmune剧目还没有详细探讨man. We描述了7个人IgM单克隆抗体的基础上选择的肺炎球菌多糖结合，共享的分子和功能特性与天然抗体，这表明一个共同的B细胞系的起源。不像类别转换抗体，这是特异性的，抗体是多反应性的，并结合所有测试的肺炎球菌多糖荚膜血清型。一些结合内源性抗原，包括血型抗原和中间丝蛋白。所有的抗体都使用未突变的重链V（IGHV），其在老年人和免疫前库中以增加的频率表达。CDR 3的特征在于长长度（平均aa 18.4（+/-4.2））和选择性使用IGHD 6（P < 0.001）和IGHJ 6（P < 0.01）家族基因。表达IGHV 1 -69和IGHV 3-21的克隆在体内提供针对侵袭性肺炎球菌疾病的显著被动保护。
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.