B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1
Details
Publication Year 2012-10-22, Volume 209, Issue #11, Page 2049-2064
Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type
Journal Article
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.
Publisher
ROCKEFELLER UNIV PRESS
Keywords
FOLLICULAR HELPER-CELL; GERMINAL CENTER B; OCTAMER-BINDING-PROTEINS; OCA-B; ANTIBODY-PRODUCTION; IMMUNE-RESPONSES; BCL6 EXPRESSION; DIFFERENTIATION; RECEPTOR; GENE
WEHI Research Division(s)
Molecular Immunology; Immunology
Rights Notice
Copyright © 2012 Karnowski et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


Creation Date: 2012-10-22 12:00:00
Last Modified: 0001-01-01 12:00:00
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