Antibodies that bind complex glycosaminoglycans accumulate in the Golgi.
Proc Natl Acad Sci U S A
; 110(29): 11958-63, 2013 Jul 16.
Article
em En
| MEDLINE
| ID: mdl-23818632
ABSTRACT
Light (L) chains that edit anti-DNA heavy (H) chains rescue B-cell development by suppressing DNA binding. However, exceptional editor L chains allow B cells to reach splenic compartments even though their B-cell receptors remain autoreactive. Such incompletely edited B cells express multireactive antibodies that accumulate in the Golgi and are released as insoluble, amyloid-like immune complexes. Here, we examine examples of incomplete editing from the analysis of variable to joining (VJ) gene junction of the variable (Vλx) editor L chain. When paired with the anti-DNA heavy chain, VH56R, the Vλx variants yield antibodies with differing specificities, including glycosaminoglycan reactivity. Our results implicate these specificities in the evasion of receptor editing through intracellular sequestration of IgM and the release of insoluble IgM complexes. Our findings can be extrapolated to human L chains and have implications for understanding a latent component of the Ig repertoire that could exert pathogenic and protective functions.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Conformação Proteica
/
Imunoglobulina M
/
Linfócitos B
/
Modelos Moleculares
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Glicosaminoglicanos
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Complexo de Golgi
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos