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

Abstract

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+ naïve 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.