Abstract
NF‐κB1‐dependent signaling directs the development of CD4^+^ Th2 cells during allergic airway inflammation and protective responses to helminth infection. Here, we show that IL‐4 and IL‐13 production is NF‐κB1‐dependent in mouse OVA‐specific CD4^+^ (OTII) T cells responding to alum‐precipitated OVA (alumOVA) immunization. More surprisingly, we found that NF‐κB1 deficiency in OTII cells also selectively impairs their CXCR5 induction by alumOVA without affecting upregulation of BCL6, IL‐21, OX40 and CXCR4 mRNA and PD‐1 protein. This results in functional impairment of follicular helper T cells. Thus, fewer germinal center B cells develop in LN responses to alumOVA in T‐cell‐deficient mice reconstituted with NF‐κB1^−/−^ OTII cells as opposed to NF‐κB1^+/+^ OTII cells, while plasma cell numbers are comparable. Unlike CXCR5 induction in CD4^+^ T cells, NF‐κB1‐deficient recirculating follicular B cells are shown to express normal levels of CXCR5. The selective effects of NF‐κB1‐deficiency on Th2 and follicular helper T cell induction do not appear to be due to altered expression of the Th2‐associated transcription factors — GATA‐3, c‐Maf and Ikaros. Altogether, these results suggest that NF‐κB1 regulates the expression of CXCR5 on CD4^+^ T cells primed in vivo, and thus selectively controls the T‐cell‐dependent germinal center component of B‐cell response to alumOVA.