The dual role of peritoneal cavity B cells in the activation of antitumor T cells

Abstract Peritoneal cavity (PerC) B cells can be classified into distinct subpopulations; however, their differential antigen-presenting capabilities and roles in antitumor immune responses remain largely unexplored. This study aimed to elucidate the properties of PerC B cell subpopulations in antitumor immune responses by using ovalbumin (OVA) peptides as neoantigen mimics and employing OT-I mice, which express a transgenic T cell receptor specific to OVA peptides. We found that OVA-pulsed PerC B cells effectively stimulated CD8+ T cell proliferation, although their antigen-presenting capacity was lower than that of splenic B cells. Subpopulation analysis revealed that CD11b+CD80+ and CD11b−CD80+ B cells produced high levels of interleukin 10 (IL-10), contributing to immunosuppressive effects. Blocking IL-10 significantly enhanced T cell proliferation and cytotoxicity, whereas PD-L1/PD-L2 blockade had no significant impact. The CD8+ T cell response in OT-I mice, stimulated by bone marrow–derived dendritic cells (BMDCs) that had phagocytosed OVA, was dose-dependently suppressed by OVA-pulsed peritoneal B cells. In an in vivo tumor model using Rag2−/− mice, co-administration of OVA-pulsed PerC B cells transiently suppressed tumor growth at lower B: T ratios but promoted tumor progression at higher B: T ratios. IL-10 knockdown in PerC B cells further enhanced tumor suppression. These findings suggest that PerC B cells exhibit a dual role in antitumor immunity, modulating CD8+ T cell responses in a density-dependent manner. While they can function as antigen-presenting cells to enhance T cell activation, their IL-10–mediated immunosuppressive properties can dampen antitumor responses. Understanding this balance may provide insights for optimizing B cell-based immunotherapies.