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

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.