IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen

Emilie Jacque, Edina Schweighoffer, Alexander Visekruna, Stamatia Papoutsopoulou, Julia Janzen, Rachel Zillwood, David M. Tarlinton, Victor L J Tybulewicz, Steven C. Ley

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

The importance of IκB kinase (IKK)-induced proteolysis of NF-κB1 p105 in B cells was investigated using Nfkb1SSAA/SSAA mice, in which this NF-κB 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-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 Nfkb1SSAA 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.

Original languageEnglish
Pages (from-to)2085-2101
Number of pages17
Journal Journal of Experimental Medicine
Volume211
Issue number10
DOIs
Publication statusPublished - 2014
Externally publishedYes

Cite this

Jacque, E., Schweighoffer, E., Visekruna, A., Papoutsopoulou, S., Janzen, J., Zillwood, R., Tarlinton, D. M., Tybulewicz, V. L. J., & Ley, S. C. (2014). IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen. Journal of Experimental Medicine, 211(10), 2085-2101. https://doi.org/10.1084/jem.20132019