Kirch S A, Rathbun G A, Oettinger M A
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
EMBO J. 1998 Aug 17;17(16):4881-6. doi: 10.1093/emboj/17.16.4881.
Immunoglobulin genes are assembled during lymphoid development by a series of site-specific rearrangements that are tightly regulated to ensure that functional antibodies are generated in B (but not T) cells and that a unique receptor is present on each cell. Because a common V(D)J recombinase comprising RAG1 and RAG2 proteins is used for both B- and T-cell antigen receptor assembly, lineage-specific rearrangement must be modulated through differential access to sites of recombination. We show here that the C-terminus of the RAG2 protein, although dispensable for the basic recombination reaction and for Ig heavy chain DH to JH joining, is essential for efficient VH to DJH rearrangement at the IgH locus. Thus, the RAG2 protein plays a dual role in V(D)J recombination, acting both in catalysis of the reaction and in governing access to particular loci.
免疫球蛋白基因在淋巴细胞发育过程中通过一系列位点特异性重排进行组装，这些重排受到严格调控，以确保在B细胞（而非T细胞）中产生功能性抗体，并且每个细胞上存在独特的受体。由于由RAG1和RAG2蛋白组成的共同V(D)J重组酶用于B细胞和T细胞抗原受体组装，因此必须通过对重组位点的差异访问来调节谱系特异性重排。我们在此表明，RAG2蛋白的C末端虽然对于基本重组反应以及Ig重链DH到JH连接是可有可无的，但对于IgH基因座处高效的VH到DJH重排至关重要。因此，RAG2蛋白在V(D)J重组中起双重作用，既参与反应的催化，又控制对特定基因座的访问。
