Manz J, Denis K, Witte O, Brinster R, Storb U
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
J Exp Med. 1988 Oct 1;168(4):1363-81. doi: 10.1084/jem.168.4.1363.
Previous work (6-10) has shown that allelic exclusion of Ig gene expression is controlled by functionally rearranged mu and kappa genes. This report deals with the comparison of membrane mu (micron) and secreted mu (microsecond) in promoting such feedback inhibition. Splenic B cell hybridomas were analyzed from transgenic mice harboring a rearranged kappa gene alone or in combination with either an intact rearranged mu gene or a truncated version of the mu gene. The intact mu gene is capable of producing both membrane and secreted forms of the protein, while the truncated version can only encode the secreted form. The role of the microsecond was also tested in pre-B cell lines. Analysis of the extent of endogenous Ig gene rearrangement revealed that (a) the production of micron together with kappa can terminate Ig gene rearrangement; (b) microsecond with kappa does not have this feedback effect; (c) microsecond may interfere with the effect of micron and kappa; and (d) the feedback shown here probably represents a complete shutoff of the specific recombinase by micron + kappa; the data do not address the question of mu alone affecting the accessibility of H genes for rearrangement.
先前的研究（6 - 10）表明，Ig基因表达的等位基因排斥受功能重排的μ和κ基因控制。本报告探讨了膜型μ（μm）和分泌型μ（μs）在促进这种反馈抑制方面的比较。对来自转基因小鼠的脾B细胞杂交瘤进行了分析，这些小鼠单独携带重排的κ基因，或与完整的重排μ基因或μ基因的截短版本组合携带。完整的μ基因能够产生该蛋白的膜型和分泌型，而截短版本只能编码分泌型。还在pre - B细胞系中测试了μs的作用。对内源Ig基因重排程度的分析表明：（a）μm与κ一起产生可终止Ig基因重排；（b）μs与κ一起不具有这种反馈作用；（c）μs可能干扰μm和κ的作用；（d）此处显示的反馈可能代表μm + κ对特异性重组酶的完全关闭；数据未涉及单独的μ影响H基因重排可及性的问题。
