Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice

Abstract

AKR mice were protected from lethal irradiation and established as long-lived chimeras by transplanting allogeneic C57BL/6 (B6) bone marrow that had been treated in vitro with anti-Thy-1 antiserum without complement. In these chimeras, which were designated [B6 .fwdarw. AKR], all thymus and spleen cells were derived from the B6 donor; several immune functions were studied in these chimeras. Chimeric mice were tolerant of histocompatibility antigens of donor and recipient strain and nearly fully reactive to antigens of third party, as revealed by Simonsen''s splenomegaly assay. Tolerance of these chimeras could not be attributed to suppressor cells but was compatible with clonal depletion. Proliferative responses to concanavalin A, phytohemagglutinin and lipopolysaccharide as well as natural killer and antibody-dependent cell-mediated cytotoxicity activity of chimeric mice was normal. Plaque-forming cell (PFC) assays of antibody responses to sheep erythrocytes (SRBC) showed gross deficiency in the primary response of the [B6 .fwdarw. AKR] and [AKR .fwdarw. B6] chimeras. By contrast, [B6-H-2k(Ek) .sbd.FAR AKR] H-2-compatible chimeras and [AKR .fwdarw. AKR] syngeneic marrow transplanted mice had normal primary PFC responses. PFC responses after secondary stimulation with SRBC revealed vigorous direct plaque formation and substantial but somewhat smaller indirect plaque formation in [B6 .fwdarw. AKR] chimeras. This observation operationally favors the concept of adaptive differentiation proposed by Katz et al. Analysis of ability of chimeras to develop and express delayed-type hypersensitivity responses to contact sensitizer (2,4-dinitro-1-fluorobenzene [DNFB]) showed no apparent immunodeficiency of either chimeras to this form of immunization. Development of immunologic tolerance to DNFB was grossly deficient in [B6 .fwdarw. AKR] chimeras but normal in [AKR .fwdarw. AKR], [B6 .fwdarw. B6] and [Ek .fwdarw. AKR] chimeras. Full chimeras across major histocompatibility complex have considerable immunologic vigor even though primary immune responses that require histocompatibility between interacting cell types are initially defective.