{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T18:48:39Z","timestamp":1792867719936,"version":"4.5.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We comprehensively characterized B cell subpopulations using single-cell RNA sequencing data from three DLBCL samples and one normal lymph tissue. The CopyKat R package was employed to assess the malignancy of B cell subpopulations based on chromosomal copy number variations. CIBERSORTx software was utilized to estimate the proportions of B cell subpopulations in 230 DLBCL tissues. Furthermore, we employed the pySCENIC to identify key transcription factors that regulate the functionality of B cell subpopulations. By employing CellphoneDB, we elucidated the interplay among tumor microenvironment components within the B cell subpopulations. Finally, we validated our findings through immunofluorescence experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis revealed a specific cancer stem cell-like B cell subpopulation exhibiting self-renewal and multilineage differentiation capabilities based on the exploration of B cell subpopulations in DLBCL and normal lymph tissues at the single-cell level. Notably, a high infiltration of cancer stem cell-like B cells correlated with a poor prognosis, potentially due to immune evasion mediated by low expression of major histocompatibility complex molecules. Furthermore, we identified key transcription factor regulatory networks regulated by <jats:italic>HMGB3<\/jats:italic>, <jats:italic>SAP30<\/jats:italic>, and <jats:italic>E2F8<\/jats:italic>, which likely played crucial roles in the functional characterization of the cancer stem cell-like B cell subpopulation. The existence of cancer stem cell-like B cells in DLBCL was validated through immunofluorescent staining. Finally, cell communication between B cells and tumor-infiltrating T cell subgroups provided further insights into the functional characterization of the cancer stem cell-like B cell subpopulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our research provides a systematic description of a specific cancer stem cell-like B cell subpopulation associated with a poor prognosis in DLBCL. This study enhances our understanding of CSCs and identifies potential therapeutic targets for refractory or recurrent DLBCL patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1310292","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T04:28:05Z","timestamp":1702268885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell 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