The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation.
Nat Genet
; 16(2): 161-70, 1997 Jun.
Article
en En
| MEDLINE
| ID: mdl-9171827
ABSTRACT
Structural alterations of the promoter region of the BCL-6 proto-oncogene represent the most frequent genetic alteration associated with non-Hodgkin lymphoma, a malignancy often deriving from germinal-centre B cells. The BCL-6 gene encodes a zinc-finger transcriptional repressor normally expressed in both B cells and CD4+ T cells within germinal centres, but its precise function is unknown. We show that mice deficient in BCL-6 displayed normal B-cell, T-cell and lymphoid-organ development but have a selective defect in T-cell-dependent antibody responses. This defect included a complete lack of affinity maturation and was due to the inability of follicular B cells to proliferate and form germinal centres. In addition, BCL-6-deficient mice developed an inflammatory response in multiple organs characterized by infiltrations of eosinophils and IgE-bearing B lymphocytes typical of a Th2-mediated hyperimmune response. Thus, BCL-6 functions as a transcriptional switch that controls germinal centre formation and may also modulate specific T-cell-mediated responses. Altered expression of BCL-6 in lymphoma represents a deregulation of the pathway normally leading to B cell proliferation and germinal centre formation.
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Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Proto-Oncogénicas
/
Células Th2
/
Proteínas de Unión al ADN
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos