Studies on autoimmunity for initiation of beta-cell destruction. X. Delayed expression of a membrane-bound islet cell-specific 38 kDa autoantigen that precedes insulitis and diabetes in the diabetes-prone BB rat.
The diabetic syndrome in the DP-BB rat results from progressive beta-cell destruction by autoimmune responses. However, the initial events causing the autoimmune destruction of beta cells remain largely unknown. Our recent experimental results suggest that the delayed expression of a beta-cell-specific autoantigen may result in the initiation of beta-cell-specific autoimmunity. The present investigation was initiated to identify such an autoantigen. Islets were isolated from DP-BB rats of several different ages, and protein extracts from the membrane fraction of the islet preparations were immunoprecipitated with sera from diabetic DP-BB rats. We have found that a membrane-bound islet cell-specific 38 kDa autoantigen is not expressed early in the life of DP-BB rats, but is delayed-expressed by approximately 30 days of age, the time at which immunological effectors begin to recognize beta cells. In contrast, a 64 kDa islet cell protein is expressed from birth in DP-BB rats. On the basis of these observations, we suggest that delayed expression of a gene encoding for the membrane-bound islet cell-specific 38 kDa autoantigen may result in a breakdown of self-tolerance, leading to beta-cell-specific autoimmune IDDM in the BB rat.
Ko
I Y
IY
Laboratory of Viral and Immunopathogenesis of Diabetes, University of Calgary, Alberta, Canada.
Jun
H S
HS
Kim
G S
GS
Yoon
J W
JW
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001324:Autoantigens / Q000032:analysis / Q000096:biosynthesis* / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002462:Cell Membrane / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007515:Islets of Langerhans / Q000254:growth & development / Q000276:immunology* / Q000473:pathology; D010182:Pancreatic Diseases / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D011913:Rats, Inbred BB; D011920:Rats, Inbred WF
D001324:Autoantigens