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This information is current as Follicular Helper CD 4 T Cell Differentiation Bcl 6 and Maf Cooperate To Instruct Human
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kroenke, Mark A. Eto, Danelle S. Locci, Michela Cho, Michael Davidson, Terence M. Haddad, Elias K. Crotty, Shane |
| Copyright Year | 2012 |
| 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. F ollicular helper CD4 T (Tfh) cells are a specialized subset of T cells that provide help to B cells (1). The defining characteristics of Tfh cells are their ability to colocalize with B cells in the follicle and their ability to provide specialized help to B cells in the form of specific cytokines and cell surface molecules. Tfh cells are required for germinal centers (GCs). In the absence of Tfh cells, severe reductions are seen in the development of Ag-specific IgG responses, memory B cells, and memory plasma cells (1). A long-term Ab response is the central attribute of most successful human vaccines (2, 3); therefore, understanding Tfh cells is important for developing truly rational vaccine-development strategies. Furthermore, Tfh cells are potentially useful biomarkers in human vaccine clinical trials. However, to harness this biology, the transcriptional control of human Tfh cell differentiation and function must be understood. Finally, several autoimmune diseases are characterized by the presence of increased GCs and autoantibodies (4, 5), which are dependent on Tfh cells in … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2012/03/16/jimmunol.1103246.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/188/8/3734.full.pdf?with-ds=yes |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/188/8/3734.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2012/03/16/jimmunol.1103246.full.pdf?with-ds=yes |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
