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 kDa protein.
BACKGROUND
We have previously reported that p53-transgenic mice are highly sensitive to low doses of a carcinogen and to vaccination with soluble 53 kDa antibodies, compared to normal mice. The splenic manifestation of this strain dependent hypersensitivity was investigated immunohistochemically and morphometrically.


METHODS
The spleen was obtained from Balb/c and human p53 promoter-CAT transgenic mice. Mice had either been treated with the carcinogen dimethylhydrazine (DMH), vaccinated before DMH treatment with polyclonal IgG generated against the soluble 53 kDa protein, or left untreated.


RESULTS
Significant differences in the splenic structures were found between the strains compared, including the area occupied by the white and red pulps, 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 and especially helper T lymphocytes was significantly lower than in Balb/c mice. Vaccination followed by DMH injections did not improve the insufficiency of the immune response in transgenic mice. In transgenic mice, the number of B lymphocytes in follicles was almost half and the total number of cells in PALS and the number of T lymphocytes were only 71% and 60% respectively in BALB/c mice. In the marginal zone, macrophages proliferated as lymphocytes decreased.


CONCLUSIONS
Insufficiency of the immune system after exposure to a carcinogen is more pronounced in transgenic mice, and is mainly related to the B-cell system. It may stem from defects in B lymphocytes or from inherent differences in their maturation and regulation. The increase in the number of macrophages, dendritic cells and neutrophils illustrates the compensatory processes that can remedy this developing immune insufficiency.
Tendler
Y
Y
Department of Clinical Biochemistry, Rambam Medical Center, Haifa, Israel.
Ben-Hur
H
H
Gurevich
P
P
Sandler
B
B
Berman
V
V
Zinder
O
O
Zusman
I
I
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D017930:Genes, Reporter; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D007116:Immunization, Passive; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012995:Solubility; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000276:immunology* / Q000502:physiology
D002273:Carcinogens; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase; D019813:1,2-Dimethylhydrazine