Denis K A, Provost S, Witte O N, Brinster R L, Storb U
Howard Hughes Medical Institute, UCLA 90024.
Dev Immunol. 1990;1(2):105-12. doi: 10.1155/1990/71584.
Mice transgenic for gamma 2b Ig heavy chain were examined for alterations in B-cell differentiation and endogenous Ig gene rearrangement and expression. Fresh bone marrow from these mice was markedly reduced in BP-1+ cells and there were small reductions in B220+ and sIg+ cells. A-MuLV (Abelson murine leukemia virus) transformants from these bone marrow cells showed little alteration in Ig gene rearrangement and expression when compared to controls, however. Isolation of the B-lymphoid compartment from these mice in vitro using LBMC (lymphoid bone marrow cultures) enabled more detailed characterization of the effects of the transgene. LBMC derived from gamma 2b transgenic mice had similar growth kinetics, but a 4-5-week delay in the expression of endogenous mu Ig in comparison to control cultures. Nucleic acids derived from these early cultures prior to endogenous mu Ig expression showed reduced Ig JH rearrangements, some sterile mu transcription, low levels of BP-1 expression, and virtually undetectable TdT (terminal deoxynucleotidyl transferase) expression. Thus, this gamma 2b transgene appears able to affect early B-lymphocyte development.
对γ2b Ig重链转基因小鼠进行了B细胞分化以及内源性Ig基因重排和表达变化的检测。这些小鼠的新鲜骨髓中BP-1+细胞显著减少,B220+和sIg+细胞也有少量减少。然而,与对照相比,来自这些骨髓细胞的A-MuLV(阿贝尔逊鼠白血病病毒)转化体在Ig基因重排和表达方面几乎没有变化。使用LBMC(淋巴样骨髓培养物)在体外分离这些小鼠的B淋巴细胞区室,能够更详细地描述转基因的作用。来自γ2b转基因小鼠的LBMC具有相似的生长动力学,但与对照培养物相比,内源性μ Ig的表达延迟了4 - 5周。在内源性μ Ig表达之前,来自这些早期培养物的核酸显示Ig JH重排减少、一些无功能的μ转录、BP-1表达水平低以及几乎检测不到的TdT(末端脱氧核苷酸转移酶)表达。因此,这种γ2b转基因似乎能够影响早期B淋巴细胞发育。