Tisch R, Roifman C M, Hozumi N
Mount Sinai Hospital Research Institute, Department of Medical Genetics and Immunology, University of Toronto, ON, Canada.
Proc Natl Acad Sci U S A. 1988 Sep;85(18):6914-8. doi: 10.1073/pnas.85.18.6914.
Crosslinked IgM molecules expressed on the surface of immature B cells mediate responses that inhibit further development, in contrast to the activational and proliferative events that follow crosslinking of the mu heavy chain in mature B cells. Concomitant with this change in IgM signaling capacity is the appearance of surface IgD, which has been proposed to modulate the response elicited by the mu heavy chain. In an attempt to gain insight into the mechanism(s) by which surface IgM is able to generate such disparate responses, delta heavy chain gene transfectants of the murine B-cell lymphoma line WEHI-231 were established. WEHI-231 cells resemble phenotypically immature B cells, in addition to being highly susceptible to the growth-inhibitory effect of surface IgM cross-linking. Endogenous mu and exogenous delta heavy chains expressed on the surface of the transfectants were compared for their role in cell proliferation and on gene expression. Our results indicate that the growth-inhibitory response is associated only with the mu heavy chain and that surface IgD does not mediate such a response. Furthermore, in contrast to IgM, IgD molecules appear to have an inductive effect on the expression of Myc and the endogenous mu and exogenous delta Ig heavy chain genes but not on the expression of the housekeeping gene encoding beta 2-microglobulin. These findings suggest that IgM and IgD are functionally distinct when expressed on the surface of an immature B cell.
与成熟B细胞中μ重链交联后引发的激活和增殖事件相反,未成熟B细胞表面表达的交联IgM分子介导的反应会抑制进一步发育。与IgM信号传导能力的这种变化同时出现的是表面IgD的出现,有人提出它可以调节由μ重链引发的反应。为了深入了解表面IgM能够产生如此不同反应的机制,建立了小鼠B细胞淋巴瘤系WEHI-231的δ重链基因转染子。WEHI-231细胞在表型上类似于未成熟B细胞,此外还对表面IgM交联的生长抑制作用高度敏感。比较了转染子表面表达的内源性μ链和外源性δ重链在细胞增殖和基因表达中的作用。我们的结果表明,生长抑制反应仅与μ重链相关,而表面IgD不介导这种反应。此外,与IgM相反,IgD分子似乎对Myc以及内源性μ链和外源性δ Ig重链基因的表达有诱导作用,但对编码β2-微球蛋白的管家基因的表达没有诱导作用。这些发现表明,当在未成熟B细胞表面表达时,IgM和IgD在功能上是不同的。