CD25+Bcl6low T follicular helper cells provide help to maturing B cells in germinal centers of human tonsil. Issue 1 (27th October 2014)

• Record Type: Journal Article
• Authors: Li, Haishan; Pauza, C. David
• Is Part Of: European journal of immunology. Volume 45:Issue 1(2015)
• Page Start: 298
• Page End: 308
• Publication Date: 2014-10-27
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201444911
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The majority of CXCR5<sup>+</sup>PD1<sup>+</sup>CD4<sup>+</sup> T follicular helper (Tfh) cells (>90%) are CD25<sup>−</sup>Bcl6<sup>hi</sup>, while a small subpopulation (<10%) are CD25<sup>+</sup>Bcl6<sup>low</sup> but do not express FoxP3 and are not T regulatory cells. We purified T:B‐cell conjugates from tonsils and found they were enriched for the CD25<sup>+</sup>Bcl6<sup>low</sup> Tfh‐cell subpopulation. In response to IL‐2, these CD25<sup>+</sup> Tfh cells increased expression of costimulatory molecules ICOS or OX40, upregulated transcription factor cMaf, produced cytokines IL‐21, IL‐17, and IL‐10, and raised the levels of antiapoptotic protein Bcl2. Conjugates formed with CD25<sup>+</sup>BCl6<sup>low</sup> Tfh cells included B cells expressing higher levels of activation‐induced cytidine deaminase (AID), memory marker CD45RO, surface IgG or IgA, and MHC class II compared to B‐cell conjugates including CD25<sup>−</sup>Bcl6<sup>hi</sup> Tfh cells. While IL‐2 suppresses early Tfh‐cell differentiation, Tfh‐cell recognition of antigen‐presenting B cells and signaling through the T‐cell receptor likely triggers expression of the high‐affinity IL‐2 receptor and responses to IL‐2 including downregulation of Bcl6. CD25 expression on Tfh cells and local production of IL‐2 in tonsil or lymph node may support B helper T‐cell function during later stages of B‐cell maturation and the development of immune memory.</p> </abstract>