First Author | Zou X | Year | 2008 |
Journal | Mol Immunol | Volume | 45 |
Issue | 13 | Pages | 3573-9 |
PubMed ID | 18584871 | Mgi Jnum | J:137831 |
Mgi Id | MGI:3803038 | Doi | 10.1016/j.molimm.2008.05.003 |
Citation | Zou X, et al. (2008) Removal of the BiP-retention domain in Cmu permits surface deposition and developmental progression without L-chain. Mol Immunol 45(13):3573-9 |
abstractText | 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, C(H)1 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 (V(H)) 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 mu 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. |