Keyna U, Beck-Engeser G B, Jongstra J, Applequist S E, Jäck H M
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
J Immunol. 1995 Dec 15;155(12):5536-42.
Bone marrow B cell precursors frequently rearrange the Ig heavy chain variable (VH) gene segment VH81X. It is puzzling, therefore, that mature B cells in adult mice rarely express mu-heavy chains bearing this VH gene segment. We show in this work in transformed pre-B cell lines that two VH81X/mu-chains that differ in their VH-D-JH joining sequences are not assembled covalently with the B cell precursor-specific surrogate light (SL) chain and are not expressed on the cell surface. From these findings, we propose that a B cell precursor clonally expands and proceeds to the next developmental stage only if it expresses a mu-chain with a VH domain that, together with the SL chain, directs the formation of a signal-transducing mu/SL chain membrane complex. Therefore, a checkpoint exists early in B cell development, at which SL chain not only screens B cell precursors for the presence of a full-length mu-chain, but also for a VH domain that promotes the assembly of a mu/SL chain complex.
骨髓B细胞前体经常重排免疫球蛋白重链可变(VH)基因片段VH81X。因此,令人费解的是,成年小鼠中的成熟B细胞很少表达携带此VH基因片段的μ重链。我们在这项针对转化前B细胞系的研究中表明,两条在VH-D-JH连接序列上不同的VH81X/μ链并非与B细胞前体特异性替代轻链(SL)链共价组装,也不在细胞表面表达。基于这些发现,我们提出,只有当B细胞前体表达的μ链具有一个VH结构域,该结构域与SL链一起指导形成信号转导μ/SL链膜复合物时,它才会进行克隆性扩增并进入下一个发育阶段。因此,在B细胞发育早期存在一个检查点,在该检查点,SL链不仅筛选B细胞前体中是否存在全长μ链,还筛选是否存在促进μ/SL链复合物组装的VH结构域。