1. Selective effects of NF-κB1 deficiency in CD4⁺ T cells on Th2 and TFh induction by alum-precipitated protein vaccines.
- Author
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Serre K, Mohr E, Bénézech C, Bird R, Khan M, Caamaño JH, Cunningham AF, and Maclennan IC
- Subjects
- Adoptive Transfer, Alum Compounds administration & dosage, Animals, B-Lymphocytes immunology, B-Lymphocytes pathology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes pathology, Cells, Cultured, Germinal Center pathology, Immunization, Lymphocyte Activation genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, NF-kappa B genetics, NF-kappa B immunology, Ovalbumin immunology, Receptors, CXCR5 genetics, Receptors, CXCR5 immunology, Th2 Cells immunology, Th2 Cells pathology, Up-Regulation genetics, B-Lymphocytes metabolism, CD4-Positive T-Lymphocytes metabolism, NF-kappa B metabolism, Receptors, CXCR5 metabolism, Th2 Cells metabolism
- 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., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2011
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