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-β1 were crucial for the MDSC-mediated promotion of IgA responses.These results demonstrate a novel mechanism of MDSC-mediated immune regulation during tumor growth.