Malynn Barbara A, Blackwell T Keith, Fulop Gabrielle M, Rathbun Gary A, Furley Andrew J, Ferrier Pierre, Heinke L Bruce, Phillips Robert A, Yancopoulos George D, Alt Frederick W
Howard Hughes Medical Institute, New York, New York.
Cell. 1988 Aug 12;54(4):453-60. doi: 10.1016/0092-8674(88)90066-9.
Abelson murine leukemia virus-transformed precursor B lymphocytes from scid (severe combined immunodeficient) mice, like A-MuLV transformants from normal mice, actively rearrange segments of their Ig heavy chain variable region gene locus during growth in culture. Targeting of recombination to appropriate segments appears normal in these lines as evidenced by initial rearrangement of sequences from within the D and JH locus to form aberrant "DJH" rearrangements and secondary rearrangement of sequences from within the VH locus to the aberrant "DJH" intermediates. A detailed analysis of the joints in these rearrangements indicates that the VDJ recombinase in scid pre-B cells can correctly recognize heptamernonamer signal sequences and perform precise endonucleolytic scissions at these sequences. We propose that the scid defect involves the inability of scid precursor lymphocytes to join correctly the cleaved ends of the coding strands of variable region gene segments.
来自严重联合免疫缺陷（scid）小鼠的艾贝尔森鼠白血病病毒转化的前体B淋巴细胞，与来自正常小鼠的A-MuLV转化体一样，在培养生长过程中会积极重排其免疫球蛋白重链可变区基因座的片段。在这些细胞系中，重组靶向适当片段的过程似乎正常，这一点可通过D和JH基因座内序列的初始重排形成异常的“DJH”重排以及VH基因座内序列与异常“DJH”中间体的二次重排得到证明。对这些重排中连接点的详细分析表明，scid前体B细胞中的VDJ重组酶能够正确识别七聚体-非聚体信号序列，并在这些序列处进行精确的内切核酸酶切割。我们提出，scid缺陷涉及scid前体淋巴细胞无法正确连接可变区基因片段编码链的切割末端。
