Novobrantseva Tatiana, Xu Shengli, Tan Joy En-Lin, Maruyama Mitsuo, Schwers Stephan, Pelanda Roberta, Lam Kong-Peng
Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany.
Int Immunol. 2005 Apr;17(4):343-50. doi: 10.1093/intimm/dxh214. Epub 2005 Feb 14.
We examined the generation and selection of the B cell antibody repertoire through crossing of mice bearing distinct Ig heavy (H) and light (L) chain rearranged variable region transgenes. Ig gene knock-in and transgenic mice whose H and L chains pair to form a non-autoreactive, functional B cell antigen receptor (BCR) have significantly reduced pre-B cells in the bone marrow as their B cell progenitors rapidly differentiate into surface IgM(+) B cells. The presence of a pre-B cell compartment in these Ig transgenic mice, however, indicates the induction of receptor editing. Here, 18 distinct combinations of H and L chains were generated that we showed could pair in vitro to form BCRs of unknown specificities. Of these, nine induced receptor editing in vivo as evidenced by the presence of pre-B cells and endogenous L chain rearrangements in mice bearing these H and L chain transgenes. These data thus suggest that about half of the emerging antibody repertoire is negatively selected during B lymphopoiesis due to the likely encoding of autoreactive or non-functional BCRs.
我们通过将携带不同免疫球蛋白重链（H）和轻链（L）重排可变区转基因的小鼠进行杂交，研究了B细胞抗体库的产生和选择。免疫球蛋白基因敲入和转基因小鼠的H链和L链配对形成非自身反应性、功能性B细胞抗原受体（BCR），其骨髓中的前B细胞显著减少，因为它们的B细胞祖细胞迅速分化为表面IgM(+) B细胞。然而，这些免疫球蛋白转基因小鼠中存在前B细胞区室，表明发生了受体编辑。在此，我们生成了18种不同的H链和L链组合，结果显示它们在体外能够配对形成特异性未知的BCR。其中，9种组合在体内诱导了受体编辑，这可通过携带这些H链和L链转基因的小鼠中存在前B细胞和内源性L链重排得以证明。因此，这些数据表明，在B淋巴细胞生成过程中，约一半新出现的抗体库因可能编码自身反应性或无功能的BCR而被阴性选择。
