Altered processing of human insulin by B lymphocytes from an immunologically insulin-resistant type I diabetic patient.
Immunologically insulin resistant (IIR) type I diabetic patients possess significantly elevated levels of anti-insulin serum autoantibodies. We investigated whether altered insulin processing by B lymphocytes contributes to this form of insulin resistance. A comparison was made of the 125I-labelled human insulin (HI) peptides processed by Epstein-Barr virus (EBV)-transformed B lymphocytes derived from HLA-identical and nonidentical IIR with non-IIR type I diabetic patients on insulin therapy and healthy non-diabetic individuals. Several peptides detected in the extracellular, membrane-associated and intracellular compartments of B cells from an IIR type I diabetic patient differed from those found in the corresponding compartments of B cells from two non-IIR type I diabetic patients and two normal individuals. These data suggest that HI is processed differently by B cells from an IIR type I diabetic patient compared with B cells from non-IIR type I diabetic patients and normal individuals. Further, we found that two of the five plasma-membrane associated processed HI peptides on the IIR patients' B cells were absent from the membrane compartments of the other B cell lines examined. Thus, it is possible that one or both of these peptides, unique to the IIR patient's B cells, consist of an immundominant epitope(s) that stimulates the production of insulin autoantibodies which mediate the onset of IIR in type I diabetes.
Semple
J W
JW
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Delovitch
T L
TL
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D002451:Cell Compartmentation; D002461:Cell Line, Transformed; D002474:Cell-Free System; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human; D006648:Histocompatibility; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007328:Insulin / Q000276:immunology / Q000378:metabolism*; D007333:Insulin Resistance / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D007328:Insulin; D010455:Peptides