title: B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1.
abstract: A strong humoral response to infection requires the collaboration of several hematopoietic cell types that communicate via antigen presentation, surface coreceptors and their ligands, and secreted factors. The proinflammatory cytokine IL-6 has been shown to promote the differentiation of activated CD4(+) T cells into T follicular helper cells (T(FH) cells) during an immune response. T(FH) cells collaborate with B cells in the formation of germinal centers (GCs) during T cell-dependent antibody responses, in part through secretion of critical cytokines such as IL-21. In this study, we demonstrate that loss of either IL-6 or IL-21 has marginal effects on the generation of T(FH) cells and on the formation of GCs during the response to acute viral infection. However, mice lacking both IL-6 and IL-21 were unable to generate a robust T(FH) cell-dependent immune response. We found that IL-6 production in follicular B cells in the draining lymph node was an important early event during the antiviral response and that B cell-derived IL-6 was necessary and sufficient to induce IL-21 from CD4(+) T cells in vitro and to support T(FH) cell development in vivo. Finally, the transcriptional activator Oct2 and its cofactor OBF-1 were identified as regulators of Il6 expression in B cells.
authors.affiliation: Molecular Immunology Division and 2 Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Karnowski
authors.forename: Stephane
authors.initials: S
authors.lastname: Chevrier
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Adele
authors.initials: A
authors.lastname: Mount
authors.forename: Dianne
authors.initials: D
authors.lastname: Emslie
authors.forename: Kathy
authors.initials: K
authors.lastname: D'Costa
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Corcoran
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050813:Octamer Transcription Factor-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D000914:Antibodies, Viral; D015850:Interleukin-6; D007378:Interleukins; D050813:Octamer Transcription Factor-2; C490424:Pou2af1 protein, mouse; C489206:Pou2f2 protein, mouse; D015534:Trans-Activators; D000098546:Interleukin-21