Zou Xiangang, Smith Jennifer A, Corcos Daniel, Matheson Louise S, Osborn Michael J, Brüggemann Marianne
The Babraham Institute, Babraham, Cambridge CB22 3AT, United Kingdom.
Mol Immunol. 2008 Aug;45(13):3573-9. doi: 10.1016/j.molimm.2008.05.003. Epub 2008 Jun 26.
Nascent, full length, immunoglobulin (Ig) heavy (H)-chains are post-translationally associated with H-chain-binding protein (BiP or GRP78) in the endoplasmic reticulum (ER). The first constant (C) domain, CH1 of a C gene (Cmu, Cgamma, Calpha), is important for this interaction. The contact is released upon BiP replacement by conventional Ig light (L)-chain (kappa or lambda). Incomplete or mutated H-chains with removed variable (VH) and/or C(H)1 domain, as found in H-chain disease (HCD), can preclude stable BiP interaction. Progression in development after the preB cell stage is dependent on surface expression of IgM when association of a micro H-chain with a L-chain overcomes the retention by BiP. We show that IgM lacking the BiP-binding domain is displayed on the cell surface and elicits a signal that allows developmental progression even without the presence of L-chain. The results are reminiscent of single chain Ig secretion in camelids where developmental processes leading to the generation of fully functional H-chain-only antibodies are not understood. Furthermore, in the mouse the largest secondary lymphoid organ, the spleen, is not required for H-chain-only Ig expression and the CD5 survival signal may be obsolete for cells expressing truncated IgM.
新生的全长免疫球蛋白（Ig）重链（H链）在翻译后与内质网（ER）中的H链结合蛋白（BiP或GRP78）相关联。C基因（Cμ、Cγ、Cα）的第一个恒定（C）结构域CH1对于这种相互作用很重要。当常规Ig轻链（L链，κ或λ）取代BiP时，这种相互作用就会解除。在重链病（HCD）中发现的去除了可变区（VH）和/或恒定区1（CH1）结构域的不完全或突变的H链，可能会阻止与BiP的稳定相互作用。前B细胞阶段之后的发育进程取决于IgM的表面表达，此时微小H链与L链的结合克服了BiP的滞留作用。我们发现，缺乏BiP结合结构域的IgM会在细胞表面展示，并引发一个信号，即使没有L链的存在，也能促进发育进程。这些结果让人联想到骆驼科动物的单链Ig分泌，在那里导致仅产生完全功能性H链抗体的发育过程尚不清楚。此外，在小鼠中，最大的二级淋巴器官脾脏对于仅表达H链的Ig并非必需，并且对于表达截短IgM的细胞，CD5存活信号可能不再需要。
