High donor regulatory B cells (Bregs) and their rapid recovery are associated with protection from the development of acute graft‐versus‐host disease (<scp>aGVHD</scp>) following allogeneic hematopoietic stem cell transplantation

This study aimed to evaluate the peripheral blood donor CD19⁺CD24^hiCD38^hi regulatory B-cell (Breg) content and the Breg recovery rates during 90 days following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their correlation with the development of acute graft-versus-host disease (aGVHD). Twenty-four donor-recipient pairs with hematological malignancies who underwent unmanipulated, fully HLA-matched allo-HSCT from related siblings were enrolled. The frequency of Bregs and their absolute number were significantly lower in donors whose recipients developed aGVHD (*p = 0.005 and *p = 0.016, respectively). Acute GVHD (+) patients had a significantly diminished percentages of Bregs recovered at days 60 and 90 compared to the aGVHD (-) ones (*p < 0.001 and *p = 0.002, respectively). A median donor Breg <1.85 as well as median Breg <1.92, <1.45, and <1.36 recovered on days 30, 60, and 90 were associated with a greater cumulative incidence of aGVHD (*p = 0.036, *p = 0.004 and *p = 0.006, respectively). Multivariate analysis revealed that infusion of grafts with a median Breg >1.85% decreased the risk of grades II-IV aGVHD (hazard ratio (HR) = 0.033, 95% confidence interval [CI] = 0.002-0.477; *p = 0.012). Our results revealed, for the first time, that high donor Breg content and their rapid recovery within 90 days after allo-HSCT were associated with a decreased risk of aGVHD.