Regulation of bifurcating B cell trajectories by mutual antagonism between transcription factors IRF4 and IRF8.
Nat Immunol
; 16(12): 1274-81, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26437243
ABSTRACT
Upon recognition of antigen, B cells undertake a bifurcated response in which some cells rapidly differentiate into plasmablasts while others undergo affinity maturation in germinal centers (GCs). Here we identified a double-negative feedback loop between the transcription factors IRF4 and IRF8 that regulated the initial developmental bifurcation of activated B cells as well as the GC response. IRF8 dampened signaling via the B cell antigen receptor (BCR), facilitated antigen-specific interaction with helper T cells, and promoted antibody affinity maturation while antagonizing IRF4-driven differentiation of plasmablasts. Genomic analysis revealed concentration-dependent actions of IRF4 and IRF8 in regulating distinct gene-expression programs. Stochastic modeling suggested that the double-negative feedback was sufficient to initiate bifurcation of the B cell developmental trajectories.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Ativação Linfocitária
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Transdução de Sinais
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Fatores Reguladores de Interferon
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article