Somatic hypermutation in T-independent and T-dependent immune responses to Haemophilus influenzae type b polysaccharide

Somatic hypermutation in T-independent and T-dependent immune responses to Haemophilus influenzae type b polysaccharide
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DOI:
10.1006/clin.1998.4603
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发表时间:
1998-12-01
期刊:
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子:
--
通讯作者:
Carroll, WL
Carroll, WL
中科院分区:
其他
文献类型:
--
作者:
Adderson, EE;Shackelford, PG;Carroll, WL

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对T非依赖性抗原的二次免疫反应的特点是很少或没有亲和力成熟,这种现象归因于有限的体细胞超突变。然而,在人类对b型流感嗜血杆菌荚膜多糖的免疫反应中,重排的重链可变区基因片段和候选种系基因之间存在许多差异,无论抗原以T非依赖性或T依赖性形式呈递。为了确定该反应中体细胞超突变的特征,我们分析了来自单克隆抗 Hib BS 抗体的重排重链可变区片段和相关的 3' 非翻译 JH4-JH5 内含子。 T非依赖性和T依赖性反应中的非翻译内含子和重链可变片段的突变类似于小鼠和未选择的人类免疫反应中所描述的突变。尽管突变在T非依赖性和T依赖性抗Hib PS反应中都很常见,但几乎没有证据表明抗原驱动的选择,这表明保存可变片段种系构型的持续压力限制了这种免疫反应中的亲和力成熟。 (C) 1998 年学术出版社。
Secondary immune responses to T-independent antigens are characterized by little or no affinity maturation, a phenomenon attributed to limited somatic hypermutation. in the human immune response to Haemophilus influenzae type b capsular polysaccharide, however, there are numerous differences between rearranged heavy chain variable region gene segments and candidate germline genes, irrespective of antigen presentation in a T-independent or T-dependent form. To determine the characteristics of somatic hypermutation in this response, we analyzed rearranged heavy chain variable region segments and associated 3' untranslated JH4-JH5 introns from monoclonal anti-Hib BS antibodies. Mutation of untranslated introns and heavy chain variable segments in both T-independent and T-dependent responses resembles that described in murine and unselected human immune responses. Although mutation is frequent in both T-independent and T-dependent anti-Hib PS responses, there is little evidence of antigen-driven selection, suggesting that ongoing pressure to conserve the variable segment germline configuration limits affinity maturation in this immune response. (C) 1998 Academic Press.