Hikida M, Ohmori H
Department of Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, Okayama 700 Japan.
J Exp Med. 1998 Mar 2;187(5):795-9. doi: 10.1084/jem.187.5.795.
V(D)J (V, variable; D, diversity; J, joining) combination of immunoglobulin (Ig) genes established in premature B cells has been thought to be conserved throughout differentiation at mature stages. However, germinal center (GC) B cells have been shown to reexpress recombination-activating gene (RAG)-1 and RAG-2 proteins in immunized mice. Here, we present several lines of evidence indicating that RAG proteins thus induced are functional as the V(D)J recombinase. DNA excision product reflecting Vlambda1 to Jlambda1 rearrangement was generated in parallel with the expression of RAG genes in mature mouse B cells that were activated in vitro with LPS and IL-4. Similar lambda chain gene rearrangement was observed in the draining lymph node of immunized mice. Further, B cells that underwent lambda gene rearrangement were shown by in situ PCR to be localized within GCs. Thus, secondary rearrangement of Ig genes (receptor editing) can occur in mature B cells.
免疫球蛋白（Ig）基因在未成熟B细胞中建立的V（D）J（V，可变区；D，多样区；J，连接区）重排，一直被认为在成熟阶段的整个分化过程中是保守的。然而，生发中心（GC）B细胞已被证明在免疫小鼠中重新表达重组激活基因（RAG）-1和RAG-2蛋白。在此，我们提供了几条证据表明，如此诱导产生的RAG蛋白作为V（D）J重组酶发挥功能。在用脂多糖（LPS）和白细胞介素-4（IL-4）体外激活的成熟小鼠B细胞中，反映Vλ1到Jλ1重排的DNA切除产物与RAG基因的表达同时产生。在免疫小鼠的引流淋巴结中观察到类似的λ链基因重排。此外，通过原位PCR显示，经历λ基因重排的B细胞定位于生发中心内。因此，Ig基因的二次重排（受体编辑）可发生在成熟B细胞中。
