The role of autoreactivity in B cell selection.
The role of autoreactivity in B cell selection.
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自身反应在 B 细胞选择中的作用。
DOI：
10.1111/j.1749-6632.1997.tb52042.x
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发表时间：
1997
影响因子：
5.2
通讯作者：
Hirabayashi,Y
中科院分区：
文献类型：
--
作者：
Stollar,BD;Lecerf,JM;Hirabayashi,Y
对IG基因组织、重排和体细胞修饰的了解提供了对抗体应答多样性的深入了解。考虑到可能的基因片段重组、连接变异、非模板核苷酸的添加和体细胞突变的数量，计算出的多样性潜力远远大于动物中B细胞的数量。因此，表达的谱系只是所有潜在序列变体的一个子集，并且在胎儿和新生儿生命中尤其受到限制！限制和塑造幼稚剧目的机制已被深入研究。自身反应性可以通过负选择来限制和塑造它，灭活或消除具有对自身抗原具有高亲和力的sIG受体的新兴B细胞，以及通过产生非自身反应性IG的二级重排（受体编辑）。8.9如果完全没有配体相互作用的新生细胞寿命很短，则会进一步缩小库。与包括β-链V区和JIL链的细胞表面IG受体的一些相互作用是B细胞通过前B细胞发育的进展所需要的，特别是在前BI和前BII阶段之间。“-14这些受体的配体尚不清楚。也许它们是内源性（即自身）配体。自身配体是否触发正信号或负信号可能取决于相互作用成分的物理形式或亲和力^*^*'^或取决于发育各个阶段可用的协作信号和信号传导途径。未成熟B细胞上受体的交联导致细胞凋亡。然而，在发育的某些阶段可能产生积极作用的自身相互作用的发生将有助于解释初级IG V基因库的非随机特征。阳性和阴性选择都可能基于自我识别的可能性是T细胞以及B细胞库发育的问题。20
Knowledge of Ig gene organization, rearrangement, and somatic modifications has provided insight into the diversity of antibody response^.'-^ Given the number of possible gene segment reassortments, junctional variations, additions of untemplated nucleotides, and somatic mutations, the calculated potential for diversity is far greater than the numbers of B cells in an animal. Thus, the expressed repertoire is only a subset of all the potential sequence variants and it is especially limited in fetal and neonatal life! Mechanisms for restricting and shaping the naive repertoire have been studied intensively. Autoreactivity can restrict and shape it through negative selection, with inactivation or elimination of emerging B cells that have sIg receptors with high affinity for auto antigen^,^-^ and through secondary rearrangements (receptor editing) that yield nonautoreactive Ig. 8.9 Further narrowing of the repertoire occurs if emerging cells that have no ligand interaction at all are short-lived.'O Some interaction with a cell surface Ig receptor that includes the p-chain V region and the JIL chain is required for progression of B cells through pre-B cell development, particularly between pre-BI and pre-BII stages."-14 The ligands for these receptors are not known. Perhaps they are endogenous (ie, self) ligands. Whether a positive or negative signal is triggered by self ligands could depend on the physical form or affinity of interacting component^*^*'^ or on the cooperating signals and signaling pathways available at various stages of deve10prnent. l~ Cross-linking of receptors on immature B cells leads to apoptosis;'8 however, the occurrence of self-interactions that might yield positive effects at some stage of development would help to explain recumng nonrandom features of the primary Ig V gene repertoire. I9 The possibility that both positive and negative selection may be based on selfrecognition is an issue for development of the T cell as well as the B cell repertoire. 20