Rudin C M, Hackett J, Storb U
Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.
J Immunol. 1991 May 1;146(9):3205-10.
Experiments with transgenic mice carrying rearranged Ig transgenes have shown that membrane bound Ig molecules cause feedback inhibition of endogenous Ig gene rearrangement. However, this inhibition is never complete. It has been postulated that escape from feedback may be a property of the Ly-1 B cell subset, whereas rearrangement of endogenous Ig genes may be completely inhibited in conventional B cells. This possibility was investigated in transgenic mice carrying a lambda transgene under the control of the H chain enhancer. It was found that kappa producing B cells in these lambda transgenic mice were for the most part, although not exclusively, of the conventional B cell phenotype. Examination of peritoneal exudate cells revealed that a large proportion of Ly-1 B cells also express kappa. Adoptive transfer of bone marrow from adult lambda transgenic mice, a source of conventional B cell precursors, resulted in the production of relatively high levels of serum kappa 2 to 3 mo after transfer into recipient SCID mice. A high proportion of donor B cells in the spleen produced endogenous kappa protein with or without co-production of lambda. It is concluded that precursors of both conventional and Ly-1 B cells can escape feedback inhibition of L chain gene rearrangement.
对携带重排Ig转基因的转基因小鼠进行的实验表明,膜结合Ig分子会对内源Ig基因重排产生反馈抑制。然而,这种抑制从未完全实现。据推测,逃避反馈可能是Ly-1 B细胞亚群的一个特性,而内源Ig基因的重排在传统B细胞中可能会被完全抑制。在携带受重链增强子控制的λ转基因的转基因小鼠中研究了这种可能性。结果发现,这些λ转基因小鼠中产生κ链的B细胞在很大程度上(尽管不是全部)具有传统B细胞表型。对腹膜渗出细胞的检查显示,很大一部分Ly-1 B细胞也表达κ链。将成年λ转基因小鼠的骨髓(传统B细胞前体的来源)进行过继转移,在转移到受体SCID小鼠后2至3个月,会产生相对高水平的血清κ链。脾脏中很大比例的供体B细胞会产生内源κ蛋白,无论是否同时产生λ链。结论是,传统B细胞和Ly-1 B细胞的前体都可以逃避轻链基因重排的反馈抑制。