{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:35:35Z","timestamp":1789608935867,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"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>Introduction<\/jats:title><jats:p>Common Variable Immunodeficiency (CVID) patients are characterized by hypogammaglobulinemia and poor response to vaccination due to deficient generation of memory and antibody-secreting B cells. B lymphocytes are essential for the development of humoral immune responses, and mitochondrial function, hreactive oxygen species (ROS) production and autophagy are crucial for determining B-cell fate. However, the role of those basic cell functions in the differentiation of human B cells remains poorly investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used flow cytometry to evaluate mitochondrial function, ROS production and autophagy processes in human na\u00efve and memory B-cell subpopulations in unstimulated and stimulated PBMCs cultures. We aimed to determine whether any alterations in these processes could impact B-cell fate and contribute to the lack of B-cell differentiation observed in CVID patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We described that na\u00efve CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>-<\/jats:sup> and memory CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> B cells subpopulations from healthy controls differ in terms of their dependence on these processes for their homeostasis, and demonstrated that different stimuli exert a preferential cell type dependent effect. The evaluation of mitochondrial function, ROS production and autophagy in na\u00efve and memory B cells from CVID patients disclosed subpopulation specific alterations. Dysfunctional mitochondria and autophagy were more prominent in unstimulated CVID CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>-<\/jats:sup> and CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> B cells than in their healthy counterparts. Although na\u00efve CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>-<\/jats:sup> B cells from CVID patients had higher basal ROS levels than controls, their ROS increase after stimulation was lower, suggesting a disruption in ROS homeostasis. On the other hand, memory CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> B cells from CVID patients had both lower ROS basal levels and a diminished ROS production after stimulation with anti-B cell receptor (BCR) and IL-21.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The failure in ROS cell signalling could impair CVID na\u00efve B cell activation and differentiation to memory B cells. Decreased levels of ROS in CVID memory CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> B cells, which negatively correlate with their <jats:italic>in vitro<\/jats:italic> cell death and autophagy, could be detrimental and lead to their previously demonstrated premature death. The final consequence would be the failure to generate a functional B cell compartment in CVID patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1362995","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T04:25:00Z","timestamp":1711427100000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Dysfunctional mitochondria, disrupted levels of reactive oxygen species, and autophagy in B cells from common variable immunodeficiency 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