B-cell receptors and heavy chain diseases: guilty by association?
Blood
; 117(26): 6991-8, 2011 Jun 30.
Article
em En
| MEDLINE
| ID: mdl-21508409
ABSTRACT
Heavy chain diseases (HCDs) are B-cell proliferative disorders characterized by the production of monoclonal, incomplete, immunoglobulin (Ig) heavy chains (HCs) without associated light chains (LCs). These abnormal HCs are produced as a consequence of HC gene alterations in the neoplastic B cells. HC gene alterations will also impact on surface HC, which is part of the B-cell receptor (BCR), a crucial player in lymphocyte activation by antigen. The selective advantage conferred to mutant cells by abnormal BCR without an antigen-binding domain may be explained by activation of ligand-independent signaling, in analogy to what has been shown for mutated oncogenic growth factor receptors. Here we review data obtained from mouse models showing abnormal, constitutive activity of HCD-BCR, and we discuss the possible mechanism involved, namely, aberrant spontaneous self-aggregation. This self-aggregation might occur as a consequence of escape from the chaperone immunoglobulin binding protein (BiP) and from the anti-aggregation effect of LC association. The concept of misfolding-induced signaling elaborated here may extend to other pathologies termed conformational diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos B
/
Doença das Cadeias Pesadas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article