B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1

Karnowski, A; Chevrier, S; Belz, GT; Mount, A; Emslie, D; D&#39;Costa, K; Tarlinton, DM; Kallies, A; Corcoran, LM

Author(s): Karnowski, A; Chevrier, S; Belz, GT; Mount, A; Emslie, D; D'Costa, K; Tarlinton, DM; Kallies, A; Corcoran, LM;
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
Research Division(s): Molecular Immunology; Immunology
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478936/
Publisher's Version: https://doi.org/10.1084/jem.20111504
Open Access at Publisher's Site: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478936/
Terms of Use/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