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T-follicular helper cell differentiation and the co-option of this pathway by non-helper cells.
MedLine Citation:
PMID:  22500838     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Summary:  Human and mouse studies performed over the last decade have established that follicular helper T (Tfh) cells are a CD4(+) helper subset specialized in the provision of help to B cells. Tfh differentiation is driven by expression of the transcriptional repressor B-cell lymphoma-6 (Bcl-6), which turns on a program that guides T cells close to B-cell areas where Tfh cells first provide help to B cells. Sustained Bcl-6 expression promotes the entry of Tfh cells into follicles and modulates their cytokine expression profile so they can support and select germinal center B cells that have acquired affinity-enhancing mutations in their immunoglobulin genes. Forkhead box 3 protein (Foxp3)(+) regulatory T cells and invariant natural killer T (NKT) cells can also co-opt the Bcl-6-dependent follicular differentiation pathway to migrate into B-cell follicles and regulate antibody responses. The resulting NKT follicular helper cells drive a distinctive type of T-dependent B-cell response to lipid-containing antigens, whereas FoxP3(+) follicular regulatory (Tfr) cells exert a suppressive function on germinal centers. Elucidating how Tfr cells are functionally and numerically regulated and the factors that control the balance between Tfh and Tfr cells is likely to be critical for improved understanding of the pathogenesis and progression of autoimmunity and lymphomas of germinal center origin, and generation of effective vaccines.
Authors:
Michelle A Linterman; Adrian Liston; Carola G Vinuesa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Immunological reviews     Volume:  247     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  143-59     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Affiliation:
Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK. VIB Autoimmune Genetics Laboratory, University of Leuven, Leuven, Belgium. John Curtin School of Medical Research, Australian National University, Canberra, Australia.
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