The shape of the lymphocyte receptor repertoire: lessons from the B cell receptor.
The shape of the lymphocyte receptor repertoire: lessons from the B cell receptor.
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DOI：
10.3389/fimmu.2013.00263
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发表时间：
2013-09-02
影响因子：
7.3
通讯作者：
Collins AM
中科院分区：
文献类型：
--
作者：
Jackson KJ;Kidd MJ;Wang Y;Collins AM
B细胞受体（BCR）和T细胞受体（TCR）库都是通过V（D）J重组、种系基因的核酸外切酶修剪和随机添加非模板编码的核苷酸的基本相同的过程产生的。幼稚TCR库受胸腺选择的限制，因此TCR库研究强烈关注MHC结合互补决定区（CDR）CDR3的多样性。体细胞点突变的过程使B细胞研究主要集中在可变基因（IGHV、IGLV和IGKV）上。这反过来又影响了对幼稚和记忆BCR库的研究。多样性（D）基因在BCR VDJ重排中也比在TCR VDJ重排中更容易识别，这使得有助于免疫球蛋白重链CDR 3难以置信的多样性的过程和元件得以详细分析。这种多样性可以与轻链的多样性形成对比，在轻链中，少量多肽序列占优势。在基因加工中使用不同种系基因以及添加非模板编码核苷酸的偏好似乎是重组过程所固有的，由于产生不同BCR的概率的差异跨越许多数量级，因此赋予重排基因库以“形状”。这可能起到增加具有重要特异性的幼稚B细胞的前体频率的作用，并参考公共和私人T细胞克隆型讨论了抗原暴露后可能出现的这种B细胞谱系。
Both the B cell receptor (BCR) and the T cell receptor (TCR) repertoires are generated through essentially identical processes of V(D)J recombination, exonuclease trimming of germline genes, and the random addition of non-template encoded nucleotides. The naïve TCR repertoire is constrained by thymic selection, and TCR repertoire studies have therefore focused strongly on the diversity of MHC-binding complementarity determining region (CDR) CDR3. The process of somatic point mutations has given B cell studies a major focus on variable (IGHV, IGLV, and IGKV) genes. This in turn has influenced how both the naïve and memory BCR repertoires have been studied. Diversity (D) genes are also more easily identified in BCR VDJ rearrangements than in TCR VDJ rearrangements, and this has allowed the processes and elements that contribute to the incredible diversity of the immunoglobulin heavy chain CDR3 to be analyzed in detail. This diversity can be contrasted with that of the light chain where a small number of polypeptide sequences dominate the repertoire. Biases in the use of different germline genes, in gene processing, and in the addition of non-template encoded nucleotides appear to be intrinsic to the recombination process, imparting “shape” to the repertoire of rearranged genes as a result of differences spanning many orders of magnitude in the probabilities that different BCRs will be generated. This may function to increase the precursor frequency of naïve B cells with important specificities, and the likely emergence of such B cell lineages upon antigen exposure is discussed with reference to public and private T cell clonotypes.
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