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

Area of Science:

• Immunology
• Cell Biology

Background:

• Tumor Necrosis Factor Receptor 2 (TNFR2) is linked to immune tolerance and suppressor cells.
• Regulatory B cells (Bregs) are crucial for controlling T cell responses and inflammation.
• TNFR2 was previously identified as a marker for IL-10-producing B cells.

Purpose of the Study:

• To investigate the role of TNFR2-expressing B cells in T cell regulation.
• To characterize the suppressive and costimulatory functions of different B cell subsets.
• To determine if TNFR2 is a reliable marker for Bregs with regulatory function.

Main Methods:

• Generation of TNFR2-positive human memory B cells using TLR9 ligand.
• Co-culture experiments involving B cells and T cells.
• Analysis of T cell proliferation and IL-10 secretion.
• Comparison of regulatory activity across different B cell populations (TNFR2+, TNFR2-, TNFR2+CD27-).

Main Results:

• TNFR2+ human memory B cells reduced T cell proliferation.
• TNFR2- and TNFR2+CD27- B cells showed costimulatory activity.
• IL-10 secretion was observed in IgM+ naïve and memory B cells, but suppressive activity was broader.
• TNFR2+ switched memory B cells and TNFR2+ IgM+ memory B cells exhibited comparable suppression despite differing IL-10 levels.
• Supernatants from TNFR2+ memory B cells did not suppress T cell proliferation, suggesting cell-contact dependent mechanisms.

Conclusions:

• Breg formation is characteristic of human memory B cells undergoing terminal differentiation.
• TNFR2 is a viable marker for identifying human memory B cells with regulatory functions.
• The suppressive function of TNFR2+ Bregs is not solely dependent on IL-10 secretion.