Immunodeficiency as primary phenotype of diabetes mutation db. Studies with coxsackievirus B4.
Restriction of food intake (R) in the C57BL/KsJ db/db diabetic mutant mouse prevents phenotypic expression of diabetes, whereas ad libitum feeding (AL) results in spontaneous diabetes. Previous results showed that coxsackievirus B4 (CB4)-infected genetically identical db/db mice with and without diabetes could be distinguished by the levels of CB4-neutralizing antibody and virus-specific antibodies as determined by enzyme-linked immunosorbent assay and the numbers of splenic antibody-forming cells. Our results show that the diabetic genotype db/db R was deficient in total spleen lymphocytes and lymphocyte subsets and was unable to produce agglutinating antibody to sheep erythrocytes (SRBCs) or specific antibody to noninfectious CB4. The db/db AL mutant expressing the diabetic phenotype was not as deficient in spleen cell parameters. The response to noninfectious CB4 was delayed but substantial. The db/db AL mouse was also unique with its higher agglutinating antibody levels after virus infection than its uninfected control or the infected or uninfected db/db R mouse. In vitro SRBC immunization of spleen lymphocytes determined that this enhanced response was largely dependent on the diabetic milieu and was not a property of the cells. Genetic predisposition to diabetes is characterized by immunodeficiency as evident from inadequate levels of antibodies to infectious or noninfectious antigens and absolute and relative deficiency in spleen lymphocyte subsets and total numbers of spleen cells. Phenotypic expression of diabetes results in partial amelioration of the immunodeficiency evident in diabetic genotype db/db R without disease.
Montgomery
L B
LB
Department of Microbiology and Immunology, School of Basic Health Sciences, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298-0678.
Loria
R M
RM
Chinchilli
V M
VM
D000818:Animals; D000921:Antibody-Producing Cells / Q000473:pathology; D003384:Coxsackievirus Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D029822:Enterovirus B, Human; D004797:Enzyme-Linked Immunosorbent Assay; D006384:Hemagglutination; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology; D007114:Immunization; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D013154:Spleen / Q000473:pathology