Scherer D C, Brockman J A, Bendall H H, Zhang G M, Ballard D W, Oltz E M
Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville Tennessee 37232, USA.
Immunity. 1996 Dec;5(6):563-74. doi: 10.1016/s1074-7613(00)80271-x.
Multiple members of the NF-kappa B/Rel protein family are induced during B cell differentiation and have been implicated in transcriptional activation of the immunoglobulin kappa (Ig kappa) locus. Despite these findings, normal numbers of Ig kappa + B lymphocytes are produced by mice bearing targeted mutations in individual NF-kappa B/Rel genes. In the present study, precursor B lymphocytes were engineered to express a trans-dominant form of I kappa B alpha that simultaneously impairs the c-Rel and RelA transactivating subunits of NF-kappa B. This dual block in NF-kappa B/Rel signaling led to potent inhibition of germline Ig kappa transcription and rearrangement, whereas recombinase activity was unaffected. These findings suggest that c-Rel and RelA serve compensatory functional roles in the developmental mechanisms that govern Ig kappa gene assembly.
NF-κB/Rel蛋白家族的多个成员在B细胞分化过程中被诱导产生，并与免疫球蛋白κ（Igκ）基因座的转录激活有关。尽管有这些发现，但携带单个NF-κB/Rel基因靶向突变的小鼠仍能产生正常数量的Igκ+B淋巴细胞。在本研究中，对前体B淋巴细胞进行基因改造，使其表达一种反式显性形式的IκBα，该形式同时损害NF-κB的c-Rel和RelA反式激活亚基。NF-κB/Rel信号传导中的这种双重阻断导致种系Igκ转录和重排受到有效抑制，而重组酶活性不受影响。这些发现表明，c-Rel和RelA在控制Igκ基因组装发育机制中发挥补偿性功能作用。
