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题目:: Human regulatory B cells control Tfh response.
作者:: Achour(Achouak),Simon(Quentin),Mohr(Audrey),Séité(Jean-François),Youinou(Pierre),Bendaoud(Boutahar),Ghedira(Ibtissem),Pers(Jacques-Olivier),Jamin(Christophe)
状态:: 发布时间2016-11-20 , 更新时间 2016-11-21
期刊:: J Allergy Clin Immunol
摘要:: Follicular 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.,To assess the role of Breg cells on Tfh development and function.,Human 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.,Bcl-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 IgDCD27 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 Foxp3CXCR5PD-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.,Human 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.
语言:: eng
DOI:: 10.1016/j.jaci.2016.09.042

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