# Tracking Extracellular Vesicles Derived From B Cells in Autoimmunity

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2022 · $242,250

## Abstract

PROJECT ABSTRACT
Immune complexes (ICs) cause inflammation and are critical for the damage of multiple organs in systemic lupus
erythematosus (SLE). Despite clear evidence linking ICs to the pathogenesis of SLE, identification of how ICs
form and the factors that influence IC localization and pathogenicity in tissues has remained elusive. Our
preliminary studies demonstrate that activated B cells secrete extracellular vesicles (EVs) that express antigen-
specific surface IgG and bind antigen. Moreover, we have identified circulating IgG+ EVs from lupus-prone mice
that bind nuclear antigens, are taken up by neutrophils, and localize to the kidney. Recent studies of SLE patients
have also identified circulating EVs that co-express IgG and nuclear antigens on their surface which correlate
with increased antinuclear antibody titers in whole plasma. Based on these data, we propose a novel hypothesis
that IgG-expressing EVs released by activated B cells upregulate inflammatory pathways either directly (i.e., as
an IC), or indirectly by interacting with a variety of cells of the innate immune system that then contribute to the
pathogenesis of lupus. We will test this hypothesis using a novel reporter mouse strain that allows for the in vivo
tracking, isolation, and functional interrogation of EVs derived from class-switched IgG+ B cells. Since little is
known about how ICs form in vivo and how they promote inflammatory immune responses in autoimmunity, we
propose a series of exploratory experiments to evaluate the intrinsic biophysical properties of B cell-derived EVs,
and the effect of B cell-derived EVs on the formation of ICs and on the control of inflammatory responses of
innate immune cells (mononuclear phagocytes; neutrophils) in healthy and autoimmune disease states. We will
use cutting-edge technologies to rigorously analyze individual B cell-derived EVs and to molecularly define the
B cell subsets that produce IgG-expressing EVs. These experiments will provide an important framework for
determining the function and disease-related dysfunction of this potentially novel mode of IC formation. Our long-
term goal is to investigate B cell-derived EVs in mediating intercellular communication, regulating deleterious
host immune responses in SLE, which may provide new therapeutic strategies to reduce inflammation and tissue
injury.

## Key facts

- **NIH application ID:** 10450549
- **Project number:** 1R21AI153990-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Loren D Erickson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,250
- **Award type:** 1
- **Project period:** 2022-01-12 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450549

## Citation

> US National Institutes of Health, RePORTER application 10450549, Tracking Extracellular Vesicles Derived From B Cells in Autoimmunity (1R21AI153990-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10450549. Licensed CC0.

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