title: Myeloid-derived suppressor cells promote B-cell production of IgA in a TNFR2-dependent manner.
abstract: 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.
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Medical Department for Gastroenterology, Infectious Diseases and Rheumatology/Research Center ImmunoSciences, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin 12200, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erben
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Peigang
authors.initials: P
authors.lastname: Wang
authors.affiliation: Medical Department for Gastroenterology, Infectious Diseases and Rheumatology/Research Center ImmunoSciences, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin 12200, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Glauben
authors.affiliation: Medical Department for Gastroenterology, Infectious Diseases and Rheumatology/Research Center ImmunoSciences, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin 12200, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Infinitus Chinese Herbal Immunity Research Centre, Guangzhou 510665, China.
authors.forename: Chung Wah
authors.initials: CW
authors.lastname: Ma
authors.affiliation: Infinitus Chinese Herbal Immunity Research Centre, Guangzhou 510665, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Hu
authors.affiliation: Infinitus Chinese Herbal Immunity Research Centre, Guangzhou 510665, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin 13125, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Jia
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin 13125, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Medical Department for Gastroenterology, Infectious Diseases and Rheumatology/Research Center ImmunoSciences, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin 12200, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D007070:Immunoglobulin A / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D047889:Receptors, Tumor Necrosis Factor, Type II; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10