IKK-induced NF-?B1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen.

ABSTRACT: The importance of I?B kinase (IKK)-induced proteolysis of NF-?B1 p105 in B cells was investigated using Nfkb1(SSAA/SSAA) mice, in which this NF-?B 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-?B 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-?B activation genetically. Our study identifies critical B cell-intrinsic functions for IKK-induced NF-?B1 p105 proteolysis in the antigen-induced survival and differentiation of FM B cells, which are essential for T-dependent antibody responses.

SUBMITTER: Jacque E 

PROVIDER: S-EPMC4172221 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature