IKK-induced NF-kappaB1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen

Jacque, E; Schweighoffer, E; Visekruna, A; Papoutsopoulou, S; Janzen, J; Zillwood, R; Tarlinton, DM; Tybulewicz, VL; Ley, SC

Author(s): Jacque, E; Schweighoffer, E; Visekruna, A; Papoutsopoulou, S; Janzen, J; Zillwood, R; Tarlinton, DM; Tybulewicz, VL; Ley, SC;
Details: Publication Year 2014-09-15,Volume 211,Issue #10,Page 2085-2101
Journal Title: J Exp Med
Publication Type: Journal Article
Abstract: The importance of IkappaB kinase (IKK)-induced proteolysis of NF-kappaB1 p105 in B cells was investigated using Nfkb1SSAA/SSAA mice, in which this NF-kappaB signaling pathway is blocked. Nfkb1SSAA mutation had no effect on the development and homeostasis of follicular mature (FM) B cells. However, analysis of mixed bone marrow chimeras revealed that Nfkb1SSAA/SSAA FM B cells were completely unable to mediate T cell-dependent antibody responses. Nfkb1SSAA mutation decreased B cell antigen receptor (BCR) activation of NF-kappaB 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 Nfkb1SSAA mutation on B cell functions were rescued by normalizing NF-kappaB activation genetically. Our study identifies critical B cell-intrinsic functions for IKK-induced NF-kappaB1 p105 proteolysis in the antigen-induced survival and differentiation of FM B cells, which are essential for T-dependent antibody responses.
Publisher: Rockefeller University Press
Research Division(s): Immunology
Publisher's Version: https://doi.org/10.1084/jem.20132019
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Creation Date: 2014-09-18 08:20:55

Last Modified: 2015-09-07 11:30:23