CD20 + FCRL4 + B Cells Activate CD8 + T Cells via MHC‐I Restriction in Nasopharyngeal Carcinoma Anti‐Tumor Immunity

ABSTRACT Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by extensive immune cell infiltration. However, the function and significance of B cells in NPC have been overlooked. Exploring B cells and their interactions with other immune cells will provide deeper insights into the immune microenvironment of NPC and theories of immunotherapy.We utilized single‐cell sequencing data to identify characteristic B cell subtypes of NPC. Subsequently, the presence of the CD20 + FCRL4 + B cell subpopulation was validated in NPC samples using immunohistochemistry and flow cytometry. The interaction between this B cell subpopulation and CD8 + T cells was investigated by establishing an in vitro and in vivo co‐culture system.Our analysis revealed a subset of CD20 + FCRL4 + B cells that may interact with CD8 + T cells through the MHC‐I pathway. Furthermore, we observed a co‐localized distribution of CD20 + FCRL4 + B cells and CD8 + T cells in NPC. Additionally, in vitro experiments demonstrated that IFNγ played a pivotal role in enhancing the delivery of MHC class I‐restricted epitope peptides by B cells, potentially due to the upregulation of WDFY4. B cells pre‐stimulated with HK‐1 lysate and IFNγ, when co‐cultured with T cells, can induce the proliferation of CD8 + T cells and the formation of immunological memory. Ultimately, this process mediates the cytotoxicity of CD8 + T cells against tumor cells both in vitro and in vivo. Notably, we found a positive correlation between the infiltration level of CD20 + FCRL4 + B cells and the expression of PD‐1, as well as the response to anti‐PD‐1 therapy or gemcitabine plus cisplatin combined with anti‐PD‐1 therapy in NPC.Overall, our study elucidates the potential anti‐tumor mechanisms of CD20 + FCRL4 + B cells and provides insights into their role in immunotherapy for NPC.