# Decoding the B cell endotype in early onset type 1 diabetes

> **NIH NIH R03** · UNIVERSITY OF COLORADO DENVER · 2021 · $147,175

## Abstract

Project Summary/Abstract
 Type 1 diabetes (T1D) is an autoimmune disorder characterized by destruction of the pancreatic beta
cells, leading to decreased production of insulin and hyperglycemia. Although T cells are the primary effectors
of beta cell destruction in T1D, autoreactive B cells are thought to be essential contributors as antigen
presenting cells. Moreover, recent findings indicate that B cells appear to play a more pathogenic role in
individuals who develop T1D at an earlier age. Studies have shown that young onset T1D subjects have
increased B cells in their blood and an increased frequency of B cells in their pancreas compared to later onset
T1D subjects. Importantly, this age-specific B cell signature is also associated with rapid progression of
disease. Despite the recent evidence for B cell participation in a more aggressive form of disease, little is
known regarding the phenotype and function of B cells in subjects at different ages of onset. Recently we
developed a robust 38+ B cell panel for high dimensional single-cell mass cytometry to simultaneously identify
total and insulin-reactive B cells, the various B cell subpopulations, and their activation and functional status,
allowing for a more granular characterization of B cells. Using this comprehensive B cell panel, in aim 1 we will
determine whether a specific B cell subset / phenotype exists in the peripheral blood of young onset T1D
subjects and a portion of at-risk autoantibody positive prediabetics, which could explain their rapid progression
of disease. In aim 2 we will compare the B cell population in paired spleen and pancreatic lymph node samples
from early onset, late onset, and control organ donors to determine whether a specific B cell subset has
migrated from the periphery (spleen) to the site of inflammation (pancreatic lymph node). The potential impact
of these studies lies in identification of the pathogenic B cell(s) responsible for the rapid progression of
disease, which will inform our understanding of the aggressiveness of early onset T1D and increase the
precision of future age appropriate therapeutics.

## Key facts

- **NIH application ID:** 10294155
- **Project number:** 1R03DK129925-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Mia Smith
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $147,175
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294155

## Citation

> US National Institutes of Health, RePORTER application 10294155, Decoding the B cell endotype in early onset type 1 diabetes (1R03DK129925-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10294155. Licensed CC0.

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