Gene expression profiling reveals B cells are highly educated by the pancreatic environment during autoimmune diabetes

Abstract

B cells play an important role in driving the development of type 1 diabetes, however, it remains unclear how they contribute to local beta-cell destruction during disease progression. Using gene expression profiling of B cell subsets in the pancreas and pancreatic lymph nodes, we reveal that B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph node. We identified both a discrete and a core shared gene expression profile in islet CD19+CD138- and CD19+CD138+ B cell subsets, the latter known to have enriched autoreactivity during diabetes development. Upon localisation to pancreatic islets, CD138+ B cells overexpressed genes associated with adhesion molecules and growth factors compared to CD138- B cells. Their shared signature displayed gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with interferon signalling pathways, pro-inflammatory cytokines and toll-like receptor activation. Finally, abundant TLR7 expression was detected in islet B cells, and was enhanced specifically in CD138+ B cells. Our study, therefore, provides a detailed transcriptional analysis of islet B cells identifying specific gene signatures and interaction networks that point towards a functional role for B cells in driving autoimmune diabetes.