TNFR2 expression is a hallmark of human memory B cells with suppressive function

Authors

TICHA Olga SLANINA Peter MOOS Lukas ŠTÍCHOVÁ Julie VLKOVÁ Marcela BEKEREDJIAN-DING Isabelle

Year of publication 2021
Type Article in Periodical
Magazine / Source EUROPEAN JOURNAL OF IMMUNOLOGY
MU Faculty or unit

Faculty of Medicine

Citation
Web https://onlinelibrary.wiley.com/journal/15214141
Doi http://dx.doi.org/10.1002/eji.202048988
Keywords B cells; Breg; IL- 10; TLR9; TNFR2
Description Tumor Necrosis Factor Receptor 2 (TNFR2) expression is increasingly being linked to tolerogenic immune reactions and cells with suppressor function including a subset of T-regulatory cells. B-regulatory cells play an important role in control of T-cell responses and inflammation. Recently, we described TNFR2 as a marker for IL-10-producing B cells, a hallmark of this cell subset. Here, we demonstrate that proliferation of T cells is reduced in the presence of TNFR2 positive human memory B cells generated with TLR9 ligand, while TNFR2- and TNFR2+CD27- B cells display costimulatory activity. Our data further reveal that IL-10 secretion is characteristic of IgM+ naive and memory B cells but suppressive activity is not restricted to IL-10: (i) the inhibitory effect of TNFR2+ switched memory B cells was comparable to that exerted by TNFR2+ IgM+ memory B cells although IL-10 secretion levels in the cocultures were lower; (ii) supernatants from TNFR2+ memory B cells failed to suppress T-cell proliferation. Based on our findings, we propose that formation of Breg is a specific characteristic of human memory B cells undergoing terminal differentiation. Our data further corroborate that TNFR2 represents a viable marker for identification of memory B cells with regulatory function.

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