A distinct follicular helper CD4 T cell programming characterizes neutralization activity in chronic HIV infection

A subset of people living with HIV (PLWH) can generate broadly neutralizing antibodies (bNAbs), yet the cellular and molecular dynamics within the lymph nodes (LNs) that facilitate this process remain unclear. To investigate these mechanisms, we performed single-cell RNA sequencing (scRNA-seq) on CD45+ cells isolated from LNs of ART-naïve PLWH who produce bNAbs. Comparative analyses revealed distinct transcriptional profiles and cellular compositions between the two groups. Our data identified potential molecular mediators of TFH-B cell interactions that are unique to neutralizers. Together, these findings provide new insights into the germinal center dynamics and immune cell networks underlying bNAb development in PLWH. Overall design: Lymph nodes from people living with HIV (PLWH) who produce broadly neutralizing antibodies (bNAbs) (n=4) and those who do not produce bNAbs (n=4) were collected. All CD45+ cells from the lymph nodes were isolated and analyzed using single-cell RNA sequencing (scRNA-seq). All PLWH were antiretroviral therapy (ART)-naive, and their bNAb repertoire was assessed prior to scRNA-seq.