title: Selective effects of NF-κB1 deficiency in CD4⁺ T cells on Th2 and TFh induction by alum-precipitated protein vaccines.
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.
authors.affiliation: MRC Centre for Immune Regulation, IBR, School of Immunity and Infection, University of Birmingham, Birmingham, UK. karine@kserre.net
authors.forename: Karine
authors.initials: K
authors.lastname: Serre
authors.forename: Elodie
authors.initials: E
authors.lastname: Mohr
authors.forename: Cécile
authors.initials: C
authors.lastname: Bénézech
authors.forename: Roger
authors.initials: R
authors.lastname: Bird
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Caamaño
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Ian C M
authors.initials: IC
authors.lastname: Maclennan
mesh_terms: D019264:Adoptive Transfer; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018858:Germinal Center / Q000473:pathology; D007114:Immunization; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000534:Alum Compounds; C513179:CXCR5 protein, mouse; D016328:NF-kappa B; D054380:Receptors, CXCR5; C041524:aluminum sulfate; D010047:Ovalbumin