Zúñiga-Pflücker J C, Jiang D, Schwartzberg P L, Lenardo M J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1994 Oct 1;180(4):1517-21. doi: 10.1084/jem.180.4.1517.
DNA recombination of the immunoglobulin (Ig) or T cell receptor (TCR) gene loci is an essential step in the production of lymphocytes bearing antigen-specific receptors. Mice that lack the ability to rearrange their Ig and TCR gene loci are devoid of mature B and T cells. Complete rearrangement and expression of the TCR-beta chain has been suggested to allow immature thymocytes to switch from the CD4-/CD8- to the CD4+/CD8+ stage of thymic development. Thus, thymocytes from severe combined immune deficient (SCID) mice or mice deficient in recombinase activation genes (RAG), which do not undergo proper DNA rearrangement, are arrested at the early CD4-/CD8- stage of development. B cell precursors in SCID or RAG mice do not progress from the B220+/sIgM-/heat stable antigen (HSA)+/CD43+ to the B220+/sIgM-/HSA+/CD43- stage. In an attempt to reconstitute RAG-2-/- mice with bone marrow- or fetal liver-derived progenitor cells, we subjected these mice to sublethal doses of gamma-radiation. It is surprising that in the absence of donor cells, irradiated RAG-2-/- mice revealed a dramatic change in their lymphoid phenotype. 14 d after irradiation, the majority of thymocytes had advanced to the CD4+/CD8+ stage of T cell development and a small number of bone marrow precursors had progressed to the CD43-, HSAhi stage of B cell development. Analysis of the resulting CD4+/CD8+ thymocytes revealed no surface expression of the TCR/CD3 complex and no V-D-J rearrangement of the TCR-beta gene locus. Our findings provide evidence for a novel pathway that allows the transition of thymocytes from the CD4-/CD8- to the CD4+/CD8+ stage and that does not appear to require TCR-beta chain rearrangement.
免疫球蛋白（Ig）或T细胞受体（TCR）基因座的DNA重组是产生携带抗原特异性受体的淋巴细胞的关键步骤。缺乏重排其Ig和TCR基因座能力的小鼠没有成熟的B细胞和T细胞。TCR-β链的完全重排和表达被认为能使未成熟胸腺细胞从胸腺发育的CD4-/CD8-阶段转变为CD4+/CD8+阶段。因此，来自严重联合免疫缺陷（SCID）小鼠或重组酶激活基因（RAG）缺陷小鼠的胸腺细胞，由于不能进行适当的DNA重排，会停滞在发育的早期CD4-/CD8-阶段。SCID或RAG小鼠中的B细胞前体不会从B220+/sIgM-/热稳定抗原（HSA）+/CD43+阶段进展到B220+/sIgM-/HSA+/CD43-阶段。为了用骨髓或胎肝来源的祖细胞重建RAG-2-/-小鼠，我们对这些小鼠进行了亚致死剂量的γ射线照射。令人惊讶的是，在没有供体细胞的情况下，受照射的RAG-2-/-小鼠的淋巴细胞表型发生了显著变化。照射后14天，大多数胸腺细胞已进展到T细胞发育的CD4+/CD8+阶段，少数骨髓前体已进展到B细胞发育的CD43-、HSAhi阶段。对产生的CD4+/CD8+胸腺细胞的分析显示，TCR/CD3复合物无表面表达，TCR-β基因座无V-D-J重排。我们的研究结果为一种新途径提供了证据，该途径能使胸腺细胞从CD4-/CD8-阶段转变为CD4+/CD8+阶段，且似乎不需要TCR-β链重排。
