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.
- MeSH
- Lymphocyte Activation genetics immunology MeSH
- B-Lymphocytes immunology metabolism MeSH
- Common Variable Immunodeficiency etiology metabolism MeSH
- Cell Differentiation immunology MeSH
- Cytokines metabolism MeSH
- Immunologic Memory * MeSH
- Immunomodulation genetics MeSH
- Interleukin-10 metabolism MeSH
- Humans MeSH
- Cell Communication immunology MeSH
- Receptors, Tumor Necrosis Factor, Type II genetics metabolism MeSH
- Gene Expression Regulation * MeSH
- B-Lymphocytes, Regulatory immunology metabolism MeSH
- Case-Control Studies MeSH
- T-Lymphocytes immunology metabolism MeSH
- Toll-Like Receptor 9 metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
