A novel type of aberrant recombination in immunoglobulin genes and its implications for V–J joining mechanism
A novel type of aberrant recombination in immunoglobulin genes and its implications for V–J joining mechanism
复制标题
免疫球蛋白基因中一种新型的异常重组及其对 V-J 连接机制的影响
作者：
J. Höchtl;H. Zachau
功能性κ轻链基因在B淋巴细胞分化过程中通过最初分离的V和J基因片段的连接形成1，2。有人认为，插入的DNA被删除了1，2，然而，最近的报道似乎是来自成熟淋巴细胞的DNA中V和J重组的相互产物（背靠背保守的V和J侧翼序列，称为f片段），使简单的删除模型不太可能3 -7。有人提出了另一种涉及姐妹染色单体交换不相等的方案5，6，证据支持f片段似乎已从携带相互完整κ轻链基因的染色体中分离出来（参考文献8简要综述了这种方案和其他方案）。我们在这里报告的分析小鼠骨髓瘤（MOPC 41），其中生产性（κ+）9和非生产性（κ-）6，10重排已经发生，这可能有助于澄清V-J连接的机制。异常重排导致J1基因片段连接到与任何V基因（L10）无关的序列，并且在生殖系中其侧翼是类似于V区重组信号序列的序列。在这种情况下，相互重组产物（κ−41和f41）的分离没有发生，这是姐妹染色单体交换模型中所需的步骤。反转模型提供了这种J重排的最简单的解释。
Functional κ light chain genes are formed during B-lymphocyte differentiation by the joining of initially separate V and J gene segments1,2. It has been suggested that the intervening DNA is deleted1,2, however the recent reports of what appear to be the reciprocal products of V and J recombination (back-to-back conserved V and J flanking sequences, called f-fragments) in DNA from mature lymphocytes make a simple deletion model unlikely3–7. An alternative scheme involving unequal sister chromatid exchange5,6 has been proposed, supported by the evidence that the f-fragments seem to have segregated from the chromosome carrying the reciprocal complete κ light chain gene (this and other schemes are briefly reviewed in ref. 8). We report here the analysis of a mouse myeloma (MOPC 41), in which a productive (κ+)9 and a non-productive (κ−)6,10 rearrangement has occurred, which may help to clarify the mechanism of V–J joining. The aberrant rearrangement has led to the joining of a J1 gene segment to a sequence unrelated to any V gene (L10), and which in the germ line is flanked by a sequence resembling a V region recombination signal sequence. In this case no segregation of the reciprocal recombination products (κ−41 and f41), which is a required step in sister chromatid exchange models, has taken place. An inversion model provides the simplest explanation of this J rearrangement.
免疫球蛋白可变区基因的定位：与免疫球蛋白基因重排的“缺失”模型的关系。
影响因子：
14.9
作者：
Selsing,E;Storb,U
通讯作者：
Storb,U