BETA-CELL MARKERS AND AUTOANTIGEN EXPRESSION BY A HUMAN INSULINOMA CELL-LINE - SIMILARITIES TO NATIVE BETA-CELLS

In the present study we have evaluated the expression of different bet a-cell markers, islet molecules and autoantigens relevant in diabetes autoimmunity by a human insulinoma cell line (CM) in order to define i ts similarities with native beta cells and to discover whether it coul d be considered as a model for studies on immunological aspects of Typ e 1 diabetes. First, the positivity of the CM cell line for known mark ers of neuroendocrine derivation was determined by means of immunocyto chemical analysis using different anti-islet monoclonal antibodies inc luding A2B5 and 3G5 reacting with islet gangliosides, and HISL19 bindi ng to an islet glycoprotein. Secondly, the expression and characterist ics of glutamic acid decarboxylase (GAD) and of GM2-1 ganglioside, bot h known to be islet autoantigens in diabetes autoimmunity and expresse d by human native beta cells, were investigated in the CM cell line. T he pattern of ganglioside expression in comparison to that of native b eta cells was also evaluated. Thirdly, the binding of diabetic sera to CM cells reacting with islet cytoplasmic antigens (ICA) was studied b y immunohistochemistry. The results of this study showed that beta cel l markers identified by anti-islet monoclonal antibodies A2B5, 3G5 and HISL-19 are expressed by CM cells; similarly, islet molecules such as GAD and GM2-1 ganglioside are present and possess similar characteris tics to those found in native beta cells; the pattern of expression of other gangliosides by CM cells is also identical to human pancreatic islets; beta cell autoantigen(s) reacting with antibodies present in i slet cell antibodies (ICA) positive diabetic sera identified by ICA bi nding are also detectable in this insulinoma cell line. We conclude th at CM cells show close similarities to native beta cells with respect to the expression of neuroendocrine markers, relevant beta cell autoan tigens in Type 1 diabetes (GAD, GM2-1, ICA antigen), and other ganglio sides. Therefore, this insulinoma cell line may be considered as an id eal model for studies aimed at investigating autoimmune phenomena occu rring in Type 1 diabetes.