Natural antibodies do not inhibit xenogeneic transplantation of human PBL in lethally irradiated mice

Abstract: Attempts to transfer human peripheral blood lymphocytes (hu-PBL) into lethally irradiated mice resulted in limited engraftment in recipients lacking natural antibodies (nAb) and could not be achieved in immunologically normal mice. It has been proposed that nAb with antihuman specificity play a major role in the rejection of the hu-PBL graft. In the present study we demonstrate that, following intensification of the conditioning protocol (thymectomy, supralethal dose of TBI, and radioprotection with bone marrow for donors with severe combined immune deficiency (SCID), transplants of 50 to 70 × 10⁶ hu-PBL were successfully engrafted in BALB/c, CBA/J and C3H/HeJ mice—regardless of the initial high levels of nAb. The percentage of human CD45⁺ cells in peritoneal lavage was not statistically different from that obtained in congenitally immune-deficient corresponding strains (SCID and CBA/N) lacking natural antibodies. Significant differences in engraftment of hu-PBL, between different human donors, were related neither to the nAb content (r = 0.29) nor to the ABO(H) blood group. The transfer of serum with high level of nAb into SCID and CBA/N mice or incubation of hu-PBL in such a serum prior to implantation, did not impede the engraftment and did not decrease the production of human immunoglobulins. These data demonstrate that the presence of nAb in supralethally irradiated normal mice does not inhibit the engraftment of hu-PBL, emphasizing the role of cellular mediated mechanisms in xenograft rejection.