Islet-infiltrating B-Cells in Nonobese Diabetic Mice Predominantly Target Nervous System Elements

Abstract

B-cells accumulate in pancreatic islets

Phenotype and Functional Characteristics of Islet-Infiltrating B-Cells Suggest the Existence of Immune Regulatory Mechanisms in Islet Milieu

“…Moreover, there were no differences in the percentage of CD5 ϩ B-cells between the islet infiltrate and the spleen. Our results are consistent with a recently published report (38) suggesting that the B-1 cell population is not present in the islet infiltrate. Only a few islet-infiltrating B-cells showed signs of activation (11% were CD69 ϩ and 7% CD86 ϩ ).…”

B Cells in Autoimmune Diabetes

“…Autoantibodies associated with other manifestations of autoimmune disease were also detected in NOD mice, including anti-thyroid antibodies and thyroiditis [20] and autoimmune hemolytic anemia [21]. In addition to production of islet cell autoantibodies in the serum, Verdaguer and colleagues have recently identified B cells infiltrating the pancreas as secreting antibodies in situ and reacting to pancreatic nervous system elements [22]. These studies complemented earlier investigations showing that, in addition to GAD, other components of cells of the nervous system are a target for attack by autoreactive T cells in diabetes [23].…”

Peripherin Is a Relevant Neuroendocrine Autoantigen Recognized by Islet-Infiltrating B Lymphocytes

“…Peripherin can be found in islet ␤ cells of mouse embryonic pancreas using histochemistry procedures, but its production in the islets of pancreas of adult mice decreases until becoming undetectable using these same procedures (9). In our previous study (16), hybridoma screening was conducted on cryosections of pancreata from adult NOD.RAG-2 Ϫ/Ϫ mice. Hence, when we screened anti-peripherin mAbs, we detected reactivity in the pancreatic nervous system, but not in islets; thus, in accordance with this neuronal staining pattern, instead of anti-neuroendocrine Abs, anti-peripherin mAbs were classified as anti-neuronal Abs.…”

“…Previously generated islet-infiltrating B cell-derived hybridomas showing neuronal staining pattern over tissue cryosections (16) were expanded and culture supernatants collected for further studies. The 21 hybridomas come from 10 independent procedures conducted using islet-infiltrating mononuclear cells from pools of pancreatic islets isolated from two to five mice.…”

“…To elucidate the antigenic repertoire of islet-infiltrating B lymphocytes, we generated hybridoma cell lines of infiltrating B lymphocytes from different mouse strains developing insulitis (16). We found that many hybridomas (56%) produced mAbs restricted to the peripheral nervous system (PNS) elements.…”