Journal article
Bcl6 and Maf Cooperate To Instruct Human Follicular Helper CD4 T Cell Differentiation
The Journal of immunology (1950), v 188(8), pp 3734-3744
15 Apr 2012
PMID: 22427637
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Follicular helper CD4 T (Tfh) cells provide B cells with signals that are important for the generation of high-affinity Abs and immunological memory and, therefore, are critical for the protective immunity elicited by most human vaccines. Transcriptional regulators of human Tfh cell differentiation are poorly understood. In this article, we demonstrate that Bcl6 controls specific gene modules for human Tfh cell differentiation. The introduction of Bcl6 expression in primary human CD4 T cells resulted in the regulation of a core set of migration genes that enable trafficking to germinal centers: CXCR4, CXCR5, CCR7, and EBI2. Bcl6 expression also induced a module of protein expression critical for T-B interactions, including SAP, CD40L, PD-1, ICOS, and CXCL13. This constitutes direct evidence for Bcl6 control of most of these functions and includes three genes known to be loci of severe human genetic immunodeficiencies (CD40L, SH2D1A, and ICOS). Introduction of Bcl6 did not alter the expression of IL-21 or IL-4, the primary cytokines of human Tfh cells. We show in this article that introduction of Maf (c-Maf) does induce the capacity to express IL-21. Surprisingly, Maf also induced CXCR5 expression. Coexpression of Bcl6 and Maf revealed that Bcl6 and Maf cooperate in the induction of CXCR4, PD-1, and ICOS. Altogether, these findings reveal that Bcl6 and Maf collaborate to orchestrate a suite of genes that define core characteristics of human Tfh cell biology. The Journal of Immunology, 2012, 188: 3734-3744.
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Details
- Title
- Bcl6 and Maf Cooperate To Instruct Human Follicular Helper CD4 T Cell Differentiation
- Creators
- Mark A. Kroenke - La Jolla Institute for ImmunologyDanelle Eto - La Jolla Institute for ImmunologyMichela Locci - La Jolla Institute for ImmunologyMichael Cho - Mission HealthTerence Davidson - University of California San DiegoElias K. Haddad - Vaccine & Gene Therapy Institute of FloridaShane Crotty - La Jolla Institute for Immunology
- Publication Details
- The Journal of immunology (1950), v 188(8), pp 3734-3744
- Publisher
- American Association of Immunologists
- Number of pages
- 11
- Grant note
- S10RR027366 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) U19AI090970 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA La Jolla Institute for Allergy and Immunology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000302641400020
- Other Identifier
- 991020100078204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology