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Abstract
NF-κB1-dependent signaling directs the development of CD4 Th2 cells during allergic airways inflammation and protective responses to helminth infection. Here, we show that IL-4 and IL-13 production is NF-κB1-dependent in mouse ovalbumin-specific CD4 (OTII) T cells responding to alum-precipitated ovalbumin (alumOVA) immunization. More surprisingly, we found that NF-κB1-deficiency in OTII cells also selectively impairs 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 (TFh) cells. Thus, fewer germinal center B cells develop in lymph node responses to alumOVA in T-cell-deficient mice reconstituted with NF-κB1OTII 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 TFh induction does 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.
Original language | English |
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Journal | European Journal of Immunology |
DOIs | |
Publication status | Published - 6 Apr 2011 |
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- 1 Finished
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A Bug in the System: How Does Salmonella Induce Novel B Cell Responses?
27/10/08 → 26/10/11
Project: Research Councils