Altered processing of human insulin by B lymphocytes from an immunologically insulinresistant type I diabetic patient

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Altered processing of human insulin by B lymphocytes from an immunologically insulinresistant type I diabetic patient. / Semple, John W.; Delovitch, Terry L.

In: Journal of Autoimmunity, Vol. 4, No. 2, 01.01.1991, p. 277-289.

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T1 - Altered processing of human insulin by B lymphocytes from an immunologically insulinresistant type I diabetic patient

AU - Semple, John W.

AU - Delovitch, Terry L.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - 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 patients' 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.

AB - 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 patients' 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.

U2 - 10.1016/0896-8411(91)90024-7

DO - 10.1016/0896-8411(91)90024-7

M3 - Article

VL - 4

SP - 277

EP - 289

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 2

ER -