Response of the spleen of Balb/c and p53-transgenic mice to low doses of carcinogen and to polyclonal antibodies generated against the soluble 53 kDaprotein

Background: We have previously reported that p53-transgenic mice air highly sensitive to low noses of a carcinogen and to vaccination with soluble 53k Da antibodies compared to normal mice. The splenic manifestation of this st rain dependent hypersensitivity was investigated immuno-histochemically and morphometrically. Methods: The spleen was obtained from Balb/c and human p 53 promoter-CAT transgenic mice. Mice had either been treated with the carc inogen dimethylhydrazine (DMH), vaccinated before DMH treatment with polycl onal IgG generated against the soluble 53 kDa protein, or left untreated. R esults: Significant differences in the splenic structures were found betwee n the strains compared, including the area occupied by the white and red pu lps, the periarterial lymphoid sheath (PALS) and the marginal zone, and in the number of lymphoblasts and lymphocytes. Exposure to DMH stimulated the immune response, but in transgenic mice the number of B and T lymphocytes a nd especially helper T lymphocytes was significantly lower than in Balb/c m ice. Vaccination followed by DMH injections did not improve the insufficien cy of the immune response in transgenic mice. In transgenic mice, the numbe r of B lymphocytes in follicles was almost half and the total number of cel ls in PALS and the number of T lymphocytes were only 71% and 60% respective ly in BALB/c mice. In the marginal zone, macrophages proliferated as lympho cytes decreased Conclusions. Insufficiency of the immune system after expos ure to a carcinogen is more pronounced in transgenic mice, and is mainly re lated to the B-cell system. It may stein from defects in B lymphocytes or f rom inherent differences in their maturation and regulation. The increase i n the number of macrophages, dendritic cells and neutrophils illustrates th e compensatory processes that can remedy this developing immune insufficien cy.