Islet beta-cytotoxic monoclonal antibody against glycolipids in experimental diabetes induced by low dose streptozotocin and Freund's adjuvant.
Diabetes was induced in BALB/c mice by four injections of a subdiabetogenic dose (40 mg/kg) of streptozotocin in combination with CFA. The treatment increased the plasma glucose from 5.8 +/- 0.1 to 22.1 +/- 1.3 mmol/liter (n = 9). The diabetic animals had circulating islet cell surface antibodies (75%), and a monoclonal islet cell surface IgM antibody, K56aF3, generated from one of the diabetic BALB/c mice, mediated C-Dependent cytotoxicity against insulin-producing cells and inhibited glucose-stimulated insulin release from isolated rat islets. Solid phase assay on thin layer chromatograms showed no binding of the K56aF3 antibody to glycolipids prepared from relevant cells. However, testing against a series of glycolipids of various non-pancreatic origins showed a preferential binding to a nine-sugar glycolipid isolated from human erythrocytes carrying an unusual blood group A determinant (type 3). It is suggested that this mAb may be associated with the development of diabetes following a combination of polyclonal activation and non-diabetogenic doses of streptozotocin.
Ziegler
M
M
Hagedorn Research Laboratory, Gentofte, Denmark.
Teneberg
S
S
Witt
S
S
Ziegler
B
B
Hehmke
B
B
Kohnert
K D
KD
Egeberg
J
J
Karlsson
K A
KA
Lernmark
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000502:physiology*; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D001666:Binding Sites, Antibody; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D004334:Drug Administration Schedule; D005620:Freund's Adjuvant / Q000008:administration & dosage*; D006017:Glycolipids / Q000276:immunology* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013311:Streptozocin / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D006017:Glycolipids; D007166:Immunosuppressive Agents; D007328:Insulin; D013311:Streptozocin; D005620:Freund's Adjuvant