Regulation of the immune response in experimental models of autoimmune disorders: Resistance of (NZB x NZW)F₁ mice to tolerance induction in vivo

Studies were carried out to test whether tolerance to alloantigens and to heterologous proteins could be induced in (NZB x NZW)F₁ (B/W) female mice, compared with females of various other mouse strains, including BALB/c, C3H/eb, C57B1/Ka and (BALB/c x C57B1/6)F₁. Untreated BALB/c and B/W mice were resistant to tolerance induction by deaggregated BSA, while all other strains were susceptible, as indicated by their lack of response to antigen challenge. Tolerance induction to BSA was further potentiated in all mouse strains including BALB/c with the exception of B/W, following prior conditioning of the mice with total lymphoid irradation (TLI). Similarly, specific and permanent tolerance to H-2 incompatible alloantigens was successfully induced in TLI conditioned BALB/c, C3H/eb, (BALB/c x C57B1/6)F₁ injected with bone marrow cells, however, B/W mice were resistant. Stable chimeras could be established in TLI treated B/W mice only across a semi-allogeneic combination (BALB/c - >B/W). No graft vs host disease (GVHD) was observed in any of the chimeras including B/W mice. We conclude that B/W mice are resistant to tolerance to heterologous proteins and alloantigens, even after TLI conditioning. We postulate that this phenomenon is a function of both the intrinsic properties of the hemopoietic stem cells, including their differentiated progeny, as well as characteristics of their cellular microenvironment.