Langman R E, Cohn M
Developmental Biology Laboratory, Salk Institute, San Diego, CA 92138-9216.
Res Immunol. 1993 Jul-Sep;144(6-7):422-46. doi: 10.1016/0923-2494(93)80126-j.
The immune system's repertoire is generated in two stages: Stage I results in a small size high copy number repertoire that is diversified by "mutation" to result in a large size low copy number repertoire referred to as Stage II. The Stage I or high copy number repertoire is derived from information stored directly in the genome by two mechanisms. (a) The copy-cassette mechanism: the Ig-locus has one rearrangeable V gene segment which acts as recipient for controlled gene conversion in cis from a set of donor V gene segments that results in a family of subunits, L and H. This is illustrated by the avian systems. (b) The cassette-exchange mechanism: the Ig-locus has many rearrangeable V gene segments which are fused into transcription units, the products of which are a family of L and H subunits identical in function to those resulting from the copy-cassette mechanism. This is illustrated by the murine or human systems. It is possible for a species to use both mechanisms, copy-cassette at one Ig locus and cassette-exchange at the other Ig locus. This seems to obtain in the rabbit system. Further, it is possible to encode the high copy number repertoire directly in the genome as tandemly repeated rearranged transcription units as one sees in shark (a genomic analogue of the cassette-exchange mechanism). We have discussed here and elsewhere (Cohn and Langman, 1990) the consequences of these mechanisms for haplotype exclusion and functional responsiveness to antigen. The Stage I or high copy number repertoire generated by any of the above mechanisms is now a substrate for "mutation" which generates the low copy number or Stage II repertoire. These three species are compared in table V. The high copy number repertoire is small but the response to any antigen that it recognizes is rapid. The low copy number repertoire is large but responsiveness to any antigen it recognizes is slow. Cooperativity between the two repertoires optimizes the overall responsiveness with respect to rapidity of response and range of responsiveness. The use of a copy-cassette mechanism requires that the phi B cell undergoing gene conversion have a single rearranged L- and H-chain haplotype (L+/oH+/o). The reason is that conversion can correct an aberrantly rearranged transcription unit and generate an unacceptable level of doubles. In order to have one chromosome functionally rearranged and the homologue in the germline configuration, a selection mechanism is required.(ABSTRACT TRUNCATED AT 400 WORDS)
第一阶段产生一个小的高拷贝数全套基因，通过“突变”使其多样化，从而产生一个大的低拷贝数全套基因，即第二阶段。第一阶段或高拷贝数全套基因通过两种机制直接从基因组中存储的信息衍生而来。(a) 拷贝盒机制：免疫球蛋白基因座有一个可重排的V基因片段，它作为顺式中受控基因转换的受体，从一组供体V基因片段接收信息，这导致了一组亚基，即轻链（L）和重链（H）。鸟类系统就是如此。(b) 盒式交换机制：免疫球蛋白基因座有许多可重排的V基因片段，它们融合成转录单位，其产物是一组轻链和重链亚基，其功能与拷贝盒机制产生的亚基相同。小鼠或人类系统就是如此。一个物种有可能同时使用这两种机制，在一个免疫球蛋白基因座使用拷贝盒机制，而在另一个免疫球蛋白基因座使用盒式交换机制。兔子系统似乎就是这样。此外，有可能像在鲨鱼中看到的那样，将高拷贝数全套基因直接编码为串联重复的重排转录单位（盒式交换机制的基因组类似物）。我们在这里以及其他地方（科恩和朗曼，1990年）讨论了这些机制对单倍型排斥和对抗原的功能反应性的影响。由上述任何一种机制产生的第一阶段或高拷贝数全套基因现在是“突变”的底物，这种“突变”产生了低拷贝数或第二阶段全套基因。表五对这三种情况进行了比较。高拷贝数全套基因数量少，但它对任何它识别的抗原的反应迅速。低拷贝数全套基因数量多，但它对任何它识别的抗原的反应缓慢。这两种全套基因之间的协同作用在反应速度和反应范围方面优化了整体反应性。使用拷贝盒机制要求进行基因转换的B细胞具有单个重排的轻链和重链单倍型（L+/oH+/o）。原因是转换可以纠正异常重排的转录单位，并产生不可接受水平的重复。为了使一条染色体功能重排而同源染色体处于种系构型，需要一种选择机制。（摘要截短于400字）
