Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity

Cell. 2020 Mar 19;180(6):1081-1097.e24. doi: 10.1016/j.cell.2020.02.015. Epub 2020 Mar 5.


Understanding molecular mechanisms that dictate B cell diversity is important for targeting B cells as anti-cancer treatment. Through the single-cell dissection of B cell heterogeneity in longitudinal samples of patients with breast cancer before and after neoadjuvant chemotherapy, we revealed that an ICOSL+ B cell subset emerges after chemotherapy. Using three immunocompetent mouse models, we recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy. By employing B-cell-specific deletion mice, we showed that ICOSL in B cells boosts anti-tumor immunity by enhancing the effector to regulatory T cell ratio. The signature of ICOSL+ B cells is imprinted by complement-CR2 signaling, which is triggered by immunogenic cell death. Moreover, we identified that CD55, a complement inhibitory protein, determines the opposite roles of B cells in chemotherapy. Collectively, we demonstrated a critical role of the B cell subset switch in chemotherapy response, which has implications in designing novel anti-cancer therapies. VIDEO ABSTRACT.

Keywords: B cell subsets; ICOSL; complement; immunogenic cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Breast Neoplasms / immunology*
  • CD55 Antigens / immunology
  • CD55 Antigens / metabolism
  • Cell Line, Tumor
  • Complement System Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand / immunology
  • Inducible T-Cell Co-Stimulator Ligand / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Complement 3d / immunology
  • Receptors, Complement 3d / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology


  • Antineoplastic Agents
  • CD55 Antigens
  • CR2 protein, human
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • Receptors, Complement 3d
  • Complement System Proteins