Human regulatory B cells control Tfh response

Publication date: Available online 16 November 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Achouak Achour, Quentin Simon, Audrey Mohr, Jean-François Séité, Pierre Youinou, Boutahar Bendaoud, Ibtissem Ghedira, Jacques-Olivier Pers, Christophe Jamin
BackgroundFollicular helper T (Tfh) cells support the terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses but their control of Tfh-dependent humoral immune responses is unknown.ObjectiveTo assess the role of Breg cells on Tfh development and function.MethodsHuman T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate Tfh cells. They were co-cultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures and their effects evaluated using flow cytometry and ELISA.ResultsBcl-6, IL-21, ICOS, CXCR5 and PD-1 expressions increased on stimulated human T cells, characterizing Tfh-cell maturation. In co-cultures, they differentiated B cells into CD138⁺ plasma and IgD^-CD27⁺ memory cells, and triggered immunoglobulin secretions. Breg cells obtained by TLR9 and CD40 activation of B cells, prevented Tfh-cell development. Added to Tfh and B cells co-cultures, they inhibited the B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3⁺CXCR5⁺PD-1⁺ follicular regulatory T (Tfr) cells. Breg cells modulated IL-21R expressions on Tfh cells and B cells, their suppressive activities involved CD40, CD80, CD86, and ICAM interactions and required production of IL-10 and TGFβ.ConclusionHuman Breg cells control the Tfh-cell maturation, expand Tfr cells and inhibit the Tfh-mediated antibody secretion. These novel observations demonstrate a role for the Breg in the germinal center reactions and suggest that deficient activities may impair the Tfh-dependent control of humoral immunity and may lead to the development of aberrant autoimmune responses.

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Teaser

Our study describes in vitro models assessing the role of human regulatory B cells to modulate Tfh cell development and function and hence, to control the humoral immune response.


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