Removal of the BiP-retention domain in Cmicro permits surface deposition and developmental progression without L-chain.
Mol Immunol
; 45(13): 3573-9, 2008 Aug.
Article
em En
| MEDLINE
| ID: mdl-18584871
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rearranjo Gênico do Linfócito B
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Cadeias Leves de Imunoglobulina
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Cadeias mu de Imunoglobulina
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Chaperonas Moleculares
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Proteínas de Choque Térmico
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Antígenos de Superfície
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article