Myeloid-derived suppressor cells promote B-cell production of IgA in a TNFR2-dependent manner

Myeloid-derived suppressor cells (MDSCs) are well known for their capacity to suppress antitumor T-cell responses, but their effects on B-cell function and antibody production remain unclear. Here, we found that MDSCs that accumulated around the germinal center in the spleen of tumor-bearing mice co-located with B cells. In the presence of MDSCs, the antibody reaction to a surrogate antigen was significantly enhanced in mice, especially the immunoglobulin (Ig) A subtype. Co-culture with MDSCs promoted both proliferation and differentiation of B cells into IgA-producing plasma cells in vitro. Interestingly, the cross talk between MDSCs and B cells required cell-cell contact. MDSCs from tumor necrosis factor receptor (TNFR) 2(-/-) mice, but not from TNFR1(-/-) mice, failed to promote B-cell responses. Further investigation suggested that interleukin-10 and transforming growth factor-beta 1 were crucial for the MDSC-mediated promotion of IgA responses. These results demonstrate a novel mechanism of MDSC-mediated immune regulation during tumor growth.