McCormack W T, Tjoelker L W, Barth C F, Carlson L M, Petryniak B, Humphries E H, Thompson C B
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor 48109.
Genes Dev. 1989 Jun;3(6):838-47. doi: 10.1101/gad.3.6.838.
The vast majority of immunoglobulin-expressing mature chicken B lymphocytes contain one functionally rearranged and one unrearranged allele of the immunoglobulin light chain (IgL) gene. Therefore, nearly all IgL V-J rearrangements present in mature chickens are in-frame. In contrast, the Ig genes of mature mammalian B cells contain a high proportion of out-of-frame V-J joints. To investigate the basis for this difference, gene rearrangement at the chicken IgL locus was characterized during embryonic development and in mature B-cell lines. Joining of the single functional variable (VL) segment with the single joining (JL) segment occurs in cells in multiple tissues during a transient period of chicken embryogenesis. Only one-third of the V-J joints cloned from days 10-12 of development are in-frame. An increasing proportion of in-frame V-J joints is observed within the bursa of Fabricius at successively later stages of development. Our data suggest that the bursa of Fabricius serves during embryonic development as a site of selective amplification of cells that have undergone productive V-J joining, such that nearly all V-J joints present in postembryonic B cells are in-frame. The high frequency of rearranged alleles joined in-frame that is found in posthatching bursal cells and mature B-cell lines appears to result from a low frequency with which cells undergo IgL rearrangement at both alleles, rather than from an increase in the precision of V-J joining in avian species.
绝大多数表达免疫球蛋白的成熟鸡B淋巴细胞含有免疫球蛋白轻链(IgL)基因的一个功能重排等位基因和一个未重排等位基因。因此,成熟鸡中几乎所有存在的IgL V-J重排都是框内的。相比之下,成熟哺乳动物B细胞的Ig基因含有高比例的框外V-J连接。为了研究这种差异的基础,在胚胎发育过程中和成熟B细胞系中对鸡IgL基因座的基因重排进行了表征。在鸡胚胎发育的一个短暂时期内,单个功能性可变(VL)片段与单个连接(JL)片段的连接发生在多个组织的细胞中。从发育第10 - 12天克隆的V-J连接中只有三分之一是框内的。在法氏囊发育的后期阶段,观察到框内V-J连接的比例不断增加。我们的数据表明,法氏囊在胚胎发育过程中作为经历了有效V-J连接的细胞的选择性扩增位点,使得胚后B细胞中几乎所有的V-J连接都是框内的。在孵化后法氏囊细胞和成熟B细胞系中发现的框内连接的重排等位基因的高频率似乎是由于细胞在两个等位基因处进行IgL重排的频率较低,而不是由于鸟类物种中V-J连接精度的提高。