IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen.
J Exp Med
; 211(10): 2085-101, 2014 Sep 22.
Article
en En
| MEDLINE
| ID: mdl-25225457
ABSTRACT
The importance of IκB kinase (IKK)-induced proteolysis of NF-κB1 p105 in B cells was investigated using Nfkb1(SSAA/SSAA) mice, in which this NF-κB signaling pathway is blocked. Nfkb1(SSAA) mutation had no effect on the development and homeostasis of follicular mature (FM) B cells. However, analysis of mixed bone marrow chimeras revealed that Nfkb1(SSAA/SSAA) FM B cells were completely unable to mediate T cell-dependent antibody responses. Nfkb1(SSAA) mutation decreased B cell antigen receptor (BCR) activation of NF-κB in FM B cells, which selectively blocked BCR stimulation of cell survival and antigen-induced differentiation into plasmablasts and germinal center B cells due to reduced expression of Bcl-2 family proteins and IRF4, respectively. In contrast, the antigen-presenting function of FM B cells and their BCR-induced migration to the follicle T cell zone border, as well as their growth and proliferation after BCR stimulation, were not affected. All of the inhibitory effects of Nfkb1(SSAA) mutation on B cell functions were rescued by normalizing NF-κB activation genetically. Our study identifies critical B cell-intrinsic functions for IKK-induced NF-κB1 p105 proteolysis in the antigen-induced survival and differentiation of FM B cells, which are essential for T-dependent antibody responses.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Transducción de Señal
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Quinasa I-kappa B
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Subunidad p50 de NF-kappa B
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Formación de Anticuerpos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido