Humoral immune response in hereditary and overt diabetes mellitus.
The inbred diabetic mutant mouse, C57BL/KsJ db +/db + (db +/db +), spontaneously develops diabetes mellitus when allowed food ad libitum. However, restriction of food intake prevents the expression of this genetic predisposition for diabetes. This experimental design has been used previously to demonstrate a deficient neutralizing antibody response to coxsackievirus B4 (CB4) in mutants with the genetic predisposition only. These observations demonstrate that in the genetically predisposed diabetic mutant, deficient humoral immunity extends further to a general impairment in both total IgM and IgG production after CB4 infection. Furthermore, these mice are unable to produce a virus-specific IgG response but do show a high level of nonspecific antibody suggesting a polyclonal activation following CB4 challenge. In addition, we observed an increase in the number of spleen IgM antibody-forming cells to sheep erythrocytes (SRBC) in the overtly diabetic animal following CB4 infection with little change apparent in the genetically predisposed animal after infection. These results were identical to the changes seen in total spleen cell numbers. Our animal model provides an opportunity to distinguish between the genetic predisposition to diabetes and the overt disease and suggests that some of the immune impairment found prior to diabetes onset may be partially diminished afterwards.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000921:Antibody-Producing Cells; D001835:Body Weight; D003384:Coxsackievirus Infections / Q000150:complications / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility; D029822:Enterovirus B, Human / Q000276:immunology; D005951:Glucose Tolerance Test; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D013154:Spleen / Q000473:pathology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M