Regulatory B cells in the blood of plasma cell hepatitis patients who have undergone liver transplantation

Abstract Alloreactive T cells and antibody-mediated rejection (AMR) appear to be barriers to long-term organ engraftment. Regulatory B cells (Bregs), a B cell subset, can protect against autoimmune/inflammatory damage, in part, by producing IL-10, an anti-inflammatory cytokine. However, the role of Bregs in solid organ transplantation is poorly understood. In this study, we examined IL-10 producing human Bregs in the blood of healthy controls compared to liver transplanted patients with plasma cell hepatitis (PCH), a variant of late onset rejection. First, we optimized conditions for human Breg differentiation in vitro. Based on the presence of differentially expressed cell surface markers on IL-10+ CD19+ B cells, we then established a profile of Bregs from several human tissues including tonsils and spleens and demonstrated that in vitro generated IL-10+CD19+ B cells are capable to suppress alloantigen stimulated T cell proliferation and cytokine production. Finally, we find that the frequency of CpG B activated IL-10+CD19+ B cells is negligible in PCH+ liver transplant patients compared with healthy controls. In line with this, the frequency of transitional B cells (CD19+CD24hiCD38hi) is significantly lower in PCH+ liver transplanted patients than healthy controls. Our findings suggest that a lack of immunosuppressive Bregs could be associated with the rejection in the PCH+ patients