Orthotopic bone transplantation in mice. II. Studies of the alloantibody response.

The alloantibody response of mice receiving cortical bone allografts was investigated. Such grafts were highly immunogenic, resulting in antibody responses at least as strong as those to skin allografts in the same combinations. The duration of the response to a single bone allograft was very prolonged (greater than 10 months). The antibody response was shown to be directed against H-2K, H-2D, Ia, and at least two non-H-2 antigens. Although the great majority of the parenchymal cells of the graft were dead, the immunogenicity of the graft required living cells, since bone that had previously been frozen and thawed was nonimmunogenic. By retransplanting bone allografts to a second recipient it was possible to demonstrate that the grafts remained immunogenic for at least 4 weeks after transplantation, indicating that the living immunogenic cells survived in the recipient for at least 4 weeks. Such cells may be certain cells of the cortical bone itself, or else residual bone marrow elements which adhere to the endosteal surface of the bone. The observation that a small subpopulation of living cells can provoke strong immune responses against a wide variety of antigens may have implications for understanding the immunogenicity of other types of allografts.