EARLY IMMUNE RECONSTITUTION OF B CELLS FOLLOWING ALLOGENEIC HAEMOPOIETIC STEM CELL TRANSPLANTATION AND THEIR RELATION TO CLINICAL OUTCOME

Abstract

Allogeneic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many haematological diseases, including both malignant and non-malignant disorders. The allogeneic immune response mediates both the beneficial graft-versus-leukaemia (GvL) effect and the detrimental graft-versus-host disease (GvHD) response. Although the balance of these responses determines the risk of early mortality and disease relapse, the immunological processes involved—including the roles of B cells in initiating and modulating alloreactive activity—have not yet been fully elucidated. In this study, the role of B cells was thoroughly investigated using various techniques, with a focus on the early period after allo-HSCT. B cells and regulatory B cells (Bregs) were phenotyped using flow cytometry–based methods. Autoantibodies were screened in allo-HSCT patients during the early post-transplant period. The B-cell transcriptome was explored using single-cell RNA sequencing (scRNA-seq). Both univariate and multivariable statistical approaches were employed to investigate significant relationships with clinical outcomes, including aGvHD, cGvHD, and disease relapse. In the B cell phenotyping study, a reduction in transitional B cells was found to be associated with the development of aGvHD. In cGvHD, a significant protective effect was observed for double-negative B cells at one month post–allo-HSCT. In the Breg study, TGF-β⁺ and GITRL⁺ transitional Bregs appeared to exert a protective effect against aGvHD, while in cGvHD, transitional Breg subsets expressing TIM-1⁺ and GITRL⁺ were also associated with a protective effect. III Additionally, autoantibodies such as anti–alpha-actinin and anti-phosphatidylserine may facilitate early prediction of cGvHD at one month post–allo-HSCT. The scRNAseq data further support these observations, indicating early pro-inflammatory signals in B cells in aGvHD and features of alloreactivity and exhaustion in B cells in cGvHD. The findings from this study highlight novel and potentially critical roles for B cells in the pathogenesis of these clinical outcomes and may identify new biomarkers or therapeutic targets.