Characteristics of somatic hypermutation of human immunoglobulin genes.
Characteristics of somatic hypermutation of human immunoglobulin genes.
复制标题
人免疫球蛋白基因体细胞超突变的特征。
DOI：
10.1007/978-3-642-71984-4_4
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发表时间：
1998
影响因子：
--
通讯作者：
Varade,WS
中科院分区：
文献类型：
--
作者：
Insel,RA;Varade,WS
免疫后抗体的亲和力成熟是免疫球蛋白基因可变区的超突变和抗原选择过程的结果，该抗原选择过程保留了那些具有突变的表面免疫球蛋白（IG）的B淋巴细胞，表达对免疫原的亲和力增加（Frenchet al.1989; KocksandRaidersky 1989; WagnerandNeuberger 1996）。然后存活的B细胞产生记忆B细胞和抗体分泌细胞。超突变是二抗应答多样化的主要机制。超突变过程不仅是谱系特异性的，而且是位点和阶段特异性的。免疫后约1-3周，次级淋巴器官生发中心的B细胞中IG基因的高突变较为突出（Levyet al. 1989;Bereket al. 1991; Rimbet al. 1991; MacLennan 1994;Pascualet al. 1994）。这些突变主要是单点置换，靶向重排的重链和轻链V基因片段的2kb DNA，在前导内含子的中间有一个尖锐的上游边界，在J-C内含子中有一个不精确的下游边界，每代每个碱基对引入约10-3-10- 4个突变，这是在真核基因组中观察到的最高突变率（KocksandRaubersky 1989; LebequeandGearhart 1990; WagnerandNeuberger 1996）。
Affinity maturation of antibodies after immunization is a result of hypermutation of the variable region of immunoglobulin genes and an antigen selection process that preserves those B lymphocytes with mutated surface immunoglobulin (Ig) expressing an increased affinity for the immunogen (Frenchet al. 1989;KocksandRajewsky1989;WagnerandNeuberger1996). The surviving B cells then give rise to memory B cells and antibody secreting cells. Hypermutation is the predominant mechanism for diversification of the secondary antibody response. The hypermutation process is not only lineage-specific but is site- and stage-specific. Hypermutation of Ig genes is prominent in B cells in the germinal centers of secondary lymphoid organs from approximately 1–3 weeks after immunization (Levyet al. 1989;Bereket al. 1991;Jacobet al. 1991;MacLennan1994;Pascualet al. 1994). The mutations are primarily single point substitutions that are targeted to 2 kb of DNA of rearranged heavy and light chain V gene segments with a sharp upstream boundary in the middle of the leader intron and an imprecise downstream boundary in the J-C intron that are introduced at approximately 10-3-10-4mutations per base pair per generation, which is the highest rate of mutation observed in the eukaryotic genome (KocksandRajewsky1989;LebequeandGearhart1990;WagnerandNeuberger1996).