IL-10+ regulatory B cells are enriched in cord blood and may protect against cGVHD after cord blood transplantation.

Cord blood (CB) offers a number of advantages over other sources of hematopoietic stem cells, including a lower rate of chronic graft-versus-host disease (cGVHD) in the presence of increased HLA disparity. Recent research in experimental models of autoimmunity and in patients with autoimmune or alloimmune disorders has identified a functional group of interleukin-10 (IL-10)-producing regulatory B cells (Bregs) that negatively regulate T-cell immune responses. At present, however, there is no consensus on the phenotypic signature of Bregs, and their prevalence and functional characteristics in CB remain unclear. Here, we demonstrate that CB contains an abundance of B cells with immunoregulatory function. Bregs were identified in both the naive and transitional B-cell compartments and suppressed T-cell proliferation and effector function through IL-10 production as well as cell-to-cell contact involving CTLA-4. We further show that the suppressive capacity of CB-derived Bregs can be potentiated through CD40L signaling, suggesting that inflammatory environments may induce their function. Finally, there was robust recovery of IL-10-producing Bregs in patients after CB transplantation, to higher frequencies and absolute numbers than seen in the peripheral blood of healthy donors or in patients before transplant. The reconstituting Bregs showed strong in vitro suppressive activity against allogeneic CD4(+) T cells, but were deficient in patients with cGVHD. Together, these findings identify a rich source of Bregs and suggest a protective role for CB-derived Bregs against cGVHD development in CB recipients. This advance could propel the development of Breg-based strategies to prevent or ameliorate this posttransplant complication.

Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation.

Cytomegalovirus (CMV) remains a major cause of morbidity following allogeneic hematopoietic stem cell transplant. Natural killer cells expressing NKG2C have been shown to play a role in the immune surveillance of human CMV. We studied NKG2C copy number in the donor graft and the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) in 100 CMV seropositive DUCBT recipients and their corresponding cord blood (CB) grafts (n = 200). In the setting of DUCBT, the combined graft may contain 0-4 functional copies of NKG2C gene. Sixteen patients received a combined graft with 1 or 2 NKG2C copies and 84 patients were recipients of a combined graft with 3 or 4 NKG2C copies. The 6-month cumulative incidence of CMV reactivation for the two groups was 93.7 and 58.4%, respectively (p = 0.0003). In multivariate analysis, low NKG2C copies in the graft was an independent predictor of CMV reactivation (HR = 2.72, CI = 1.59-4.64; p < 0.0001). Our study points to an important role for donor NKG2C for protection against CMV reactivation after DUCBT. These novel findings may help identify patients at a higher risk of CMV reactivation after DUCBT. Donor NKG2C genotype may be used as a potential criterion in the algorithm for graft selection for DUCBT.