Naive B cells with low differentiation improve the immune reconstitution of HIV-infected patients

Incomplete immune reconstitution happens in some HIV-infected patients who have achieved persistent viral suppression under antiretroviral therapy (ART). We performed single-cell F'-NA sequencing for peripheral blood mononuclear cells to analyze B cell receptor (BCR) repertoire and B cell subtypes in health controls (non-HIV-infected, HCs), HIV-infected immunological responders (IRs), and immunological nonresponders (INRs). We found that the dominant usage of IGHV gene segrients of naive B cells and memory B cells were IGHV3 and IGHV4, and the diversity of BCR repertoire was decreased in INRs. Differentiation trajectory analysis showed that the low differentiation of naive B cells was related to satisfactory immune status. The cell cycle of B cells with immune-specific genes of IgD(+) B cells was degraded in INRs, which was medi ted by the anaphase-promcting complex/cyclosome pathway in the phase of G2/M checkpoints. These findings provide significant insights to understand the function of B cell-mediated immune response in immune reconstitution after HIV infection.