Improved immune function with donor B-cell infusion after semi-allogeneic bone marrow transplantation in mice

Regeneration of the immune system after bone marrow transplantation (BMT) is a slow process, often prolonged by the development and treatment of graft vs. host disease (GVHD). Donor lymphocyte infusion using allogeneic T-cells is widely applied for the induction of GVHD, which is associated with the desired graft vs. leukemia effect. Due to the slow immune recovery, our objective was to accelerate the immune recovery post-BMT by B-cell injections.

T-cell-depleted stem cells obtained from female C57BL/6 (B6) mice were transplanted into lethally irradiated (Balb/c x C57BL/6) F-1 female mice. Seven days post-transplantation, murine B-cells of male C57BL/6 origin were infused into the T-cell-depleted chimeras. Thirty and 60 days post-transplantation, PCR analysis of the Y-chromosome was carried out to detect male B-cells in the transplant recipients. In order to evaluate the specific antibody response, the donors were immunized by specific T-cell-dependent and -independent antigens.

None of the T-cell-depleted transplanted mice developed GVHD during a follow-up period of 650 days, whereas all non-T-cell-depleted recipients died. At 60 days post-transplantation, significantly higher levels of immunoglobulins (IgA, IgG1, IgG3 isotypes) were seen in chimeras supplemented with male B-cells than in chimeras reconstituted with T-cell-depleted stem cells alone.

Our data document the feasibility of administering B-cell therapy post-allogeneic BMT to improve recovery of the humeral arm of the immune system while avoiding GVHD. Furthermore, post-transplant B-cell administration may have an important impact as an alternative to IV immunoglobulin infusions.