Reconstitution of peripheral allospecific CD19+ B-cell subsets after B-lymphocyte depletion therapy in renal transplant patients.

Background: Desensitization protocols, which frequently use lymphocyte depleting agents have increased access to successful transplantation for sensitized candidates. Here, we report on the reconstitution of human leukocyte antigen (HLA)-specific B lymphocytes in renal transplant patients after treatment with B-lymphocyte depletion.

Methods: Sixteen renal transplant candidates were included in the study. Eleven patients were treated with anti-CD20 monoclonal antibody (Ab), four of whom also underwent splenectomy perioperatively. Five patients who did not undergo B-cell depletion were studied as controls. Blood samples were obtained before any treatment and transplant, and at later time points up to 44 months posttransplant. HLA-specific B-cell subpopulations were identified by staining with fluorochrome-labeled HLA tetramers and anti-CD19, CD27, and CD38 monoclonal Abs.

Results: Total circulating B lymphocytes repopulated within 12 months post-B-cell depletion. The majority of the recovering cells had the phenotype of transitional CD38 B cells and the percentages of mature, memory CD27 B cells remained significantly depressed. There was a sustained reduction in the proportion of HLA-specific CD27 memory B cells, whereas the HLA-specific CD38 B-cell population returned to near pretreatment levels by 12 months. The presence of mismatched HLA antigens seemed to affect the reconstitution kinetics. The delay in reconstitution of HLA-specific CD27 memory B cells was greater for donor-specific compared with third party.

Conclusions: A delay in functional maturity of repopulating HLA-specific B cells, and in particular those specific for donor HLA, after B-lymphocyte depletion treatment in renal transplant recipients may contribute to the efficacy of desensitization protocols.