AIRRC7 - Identification of pathogenic B cells in type 1 diabetes (N. Luning Prak)

"Identification of pathogenic B cells in type 1 diabetes"
Nina Luning Prak, University of Pennsylvania, Professor

In type 1 diabetes (T1D), T cells, helped by autoreactive B cells, destroy the insulin-producing beta cells in the pancreas. The identification of pathogenic B cells could facilitate earlier disease detection and intervention that may delay or prevent autoimmune attack before organ damage. To that end, we are using immune repertoire profiling approaches to identify and characterize tissue-based B cells in organ donors with and without T1D. Leveraging tissue samples and extensively phenotyped organ donors from the human pancreas analysis program, we are studying clonal networks of B cells in pancreatic lymph node (PLN), mesenteric lymph node and spleen of organ donors with and without T1D to identify and characterize tissue-resident B cell populations. This analysis has generated thousands of tissue-spanning clones and candidate clones of interest that are large and enriched in PLN. Coupled with cell sorting and single cell analysis, we are further studying clones that reside in memory B cell subsets. In parallel, we are studying autoantigen-enriched B cell populations and isolating monoclonal antibodies of autoantigen-binding B cells. Finally, we are tracking candidate clones derived from both of these approaches through immune repertoires of different individuals to search for repertoire motifs that may distinguish T1D autoimmunity from health.

AIRR Community Meeting VII – Learnings and Perspectives
June 3-6, 2024
University of Porto, Porto, Portugal
https://www.antibodysociety.org/the-a...