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.