Regulatory B cells promote graft-versus-host disease prevention and maintain graft-versus-leukemia activity following allogeneic bone marrow transplantation

ABSTRACT

Regulatory B cells (Bregs) are involved in the pathogenesis of graft-versus-host disease (GVHD). However, whether Bregs can alleviate acute GVHD without compromising graft-versus-leukemia (GVL) effects remains unclear. Here, we evaluated the role of Bregs in acute GVHD and GVL activity in both a mouse model and a clinical cohort study. In the acute GVHD mouse model, co-transplantation of Bregs prevents onset through inhibiting Th1 and Th17 differentiation and expanding regulatory T cells. In the GVL mouse model, Bregs contributed to the suppression of acute GVHD but had no adverse effect on GVL activity. In the clinical cohort study, a higher dose of Bregs in allografts was associated with a lower cumulative incidence of acute GVHD but not with increased risk of relapse. Our data demonstrate that Bregs can prevent acute GVHD and maintain GVL effects and suggest that Bregs have potential as a novel strategy for acute GVHD alleviation.

KEYWORDS:

• Allogeneic stem cell transplantation
• graft-versus-host disease
• graft-versus-leukemia effects
• regulatory B cells
• Th cells

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank all of the faculty members who participated in these studies. We would also like to thank San Francisco Edit (www.sefedit.net) for assistance in editing this manuscript.

Funding

This work was supported (in part) by the National Natural Science Foundation of China (Grant Nos. 81470342; 81670168), the Key Program of the National Natural Science Foundation of China (Grant No. 81230013), the Beijing Natural Science Foundation (7162196), and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 81621001).

Author contributions

Contribution: X.-J.H. designed the study; Y.-J.C. and Y. H. collected data; Y.H., Y.-J.C., and X.-J.H. analyzed the data and drafted the manuscript; and all authors contributed to data interpretation, manuscript preparation, and approval of the final version.