CD9⁺ B Cells Induce T Follicular Helper Cell Apoptosis to Regulate Germinal Center Regression

Adenoid hypertrophy (AH) is associated with excessive proliferation of germinal center B (GC-B) cells, yet the mechanisms underlying GC regression and termination remain poorly understood. This study used single-cell RNA sequencing (scRNA-seq) to profile the cellular composition of GC-B cells in AH. A unique subset of GC-B cells expressing CD9 was identified through comprehensive scRNA-seq, flow cytometry, and Mass cytometry (CyToF) analyses, with subsequent studies assessing the roles of CD9 and FOXP1 in GC-B cell differentiation and apoptosis pathways. CD9⁺ B cells were detected throughout GC-B cell development and were regulated by FOXP1. These cells also exhibited activation of cell death-related pathways, particularly during adenoid development. AH samples showed an increase in T follicular helper (Tfh) cells, accompanied by a reduction in CD9⁺ B cells. In Cd9 knockout mice, CD9 deficiency led to a significant decrease in serum IgG levels. Further analysis revealed that CD9⁺ B cells promoted Tfh cell apoptosis via pathways such as ALCAM-CD6. CD9⁺ B cells may regulate GC-B cell regression by inducing Tfh cell apoptosis, and FOXP1 may play a role in their differentiation. These findings clarify mechanisms of GC degeneration and termination, offering potential targets for AH treatment.