Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice.
Antinuclear autoantibodies (ANA) appeared in the plasma of lethally irradiated H-2d histocompatible DBA/2 and BALB/c mice several weeks after intravenous transplantation of 2 to 4 x 10(6) bone marrow cells from 3-week-old animals of the autoimmune New Zealand Black (NZB) strain. Little or no ANA development was observed in DBA/2 or BALB/c strains when syngeneic or nonautoimmune allogeneic marrow was grafted, or when NZB marrow was injected into untreated DBA mice or mice receiving 200 rads of x-irradiation. Transfer of 5 x 10(6) spleen cells from 8-day-old NZB mice into lethally irradiated BALB/c mice effected substantial ANA formation by the ninth day after transfer, compared to a 20-day latency following transfer of the same number of bone marrow cells. This earlier conversion with splenocytes may have been due to the presence of immunocompetent T and B cells, since stem cell numbers of the two tissues were similar. Transplantation of NZB marrow to lethally irradiated H-2 incompatible SJL/J (H-2s) and C57B1/6 (H-2b) strains brought about less ANA conversion than the transfer of compatible (SJL x NZB)F1 and (C57B1 x NZB)F1 marrow cells to the respective nonautoimmune SJL or C57B1 parental strain. Graft-versus-host reactions thus did not appear to play a requisite or determining role in the autoimmune development observed following grafting of NZB hemopoietic tissues. Reconstitution of lethally irradiated NZB mice with BALB/c or SJL/J bone marrow depressed the recurrence of ANA for 30 days, compared to rapid ANA recovery following NZB marrow injection. The characteristics that ultimately provoke or permit spontaneous auto-reactivity are inherent in the hemopoietic stem cell population of the NZB strain.
D000818:Animals; D000974:Antibodies, Antinuclear; D000917:Antibody Formation; D001323:Autoantibodies; D001327:Autoimmune Diseases / Q000276:immunology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D006412:Hematopoietic Stem Cells; D006648:Histocompatibility; D007112:Immunity, Maternally-Acquired; D007116:Immunization, Passive; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology; D014184:Transplantation, Homologous
D000974:Antibodies, Antinuclear; D001323:Autoantibodies