Autologous hematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patients.

OBJECTIVES The rationale of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases is that high-dose immunosuppression eradicates autoreactive T and B cells, and the infused autologous hematopoietic stem cells promote reconstitution of a naive and self-tolerant immune system. The aim of this study was to evaluate the reconstitution of different B cell subsets, both quantitatively and functionally, in systemic sclerosis (SSc) patients treated with AHSCT. METHODS Peripheral blood was harvested from twenty-two SSc patients before transplantation and at 30, 60, 120, 180 and 360 days post-AHSCT. Immunophenotyping of B cell subsets, B cell cytokine production, signaling pathways, and suppressive capacity of regulatory B cells (Bregs) were assessed by flow cytometry. RESULTS Naive B cell frequencies increased from 60 to 360 days post-AHSCT, compared to pre-transplantation. Conversely, memory B cell frequencies decreased during the same period. Plasma cell frequencies transiently decreased at 60 days post-AHSCT. IL-10-producing Bregs CD19+CD24hiCD38hi and CD19+CD24hiCD27+ frequencies increased at 180 days. Moreover, the phosphorylation of ERK1/2 and p38MAPK proteins increased in B cells reconstituted post-AHSCT. Notably, CD19+CD24hiCD38hi Bregs recovered their ability to suppress production of Th1 cytokines by CD4+ T cells at 360 days post-AHSCT. Finally, IL-6 and TGF-β1-producing B cells decreased following AHSCT. CONCLUSION Taken together, these results suggest improvements in immunoregulatory and anti-fibrotic mechanisms after AHSCT for SSc, which may contribute to reestablishment of self-tolerance and clinical remission.