Abstract Text: Transplanted patients tolerating a kidney graft without immunosuppression (TOL) display a higher number of circulating regulatory B cells, acting through a granzyme B (GZMB)-dependent manner. IgA+ plasmablasts/plasma cells have been associated with regulatory B cells secreting IL-10, but nothing is known regarding GZMB+ Bregs. The objective was to explore a potential link between IgA and GZMB+ B cells in non-transplanted (HV) and kidney-transplanted patients (KTP). Patients with: stable kidney graft function under immunosuppression, progressive degradation of kidney function, stable kidney graft function under one immunosuppressive drug, TOL patients and HV volunteers were included. The quantification, subclasses and glycosylation levels of IgA were determined by ELISA, IgA forms by Western blot; scRNAseq was performed on GZMB+ Bregs, multiparametric flow cytometry analysis on patient PBMC. The suppressive properties of IgA+ B cells were analyzed in B-T cell co-cultures. We showed that IgA blood levels were increased in TOL patients, with a significant increase of IgA1. There was no change in the forms or glycosylation level of IgA between KTP. Transcriptomic analysis revealed higher IgA expression in GZMB+ Bregs and, conversely, higher GZMB expression in IgA+ B cells. Flow cytometry analysis showed a higher expression of GZMB in IgA+ B cells from TOL compared with other KTP. Finally, IgA+ B cells demonstrated higher T-cell suppressive properties than IgA- B cells and total B cells. These findings suggest a strong link between IgA+ and GZMB+ B cells in TOL patients with increased IgA1 frequency, higher GZMB and IgA expression and higher suppressive properties.
