# Autoimmunity-Associated B Cells in Lupus Nephritis

> **NIH NIH K08** · UNIVERSITY OF ROCHESTER · 2024 · $192,240

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal details a five-year research and career development plan with a scientific focus on
autoimmunity-associated B cells (ABC), a subset of cells that is expanded during lupus disease activity and
can differentiate into autoantibody-producing plasma cells (PC). These cells are found in the kidneys of lupus
nephritis patients.
The long-term objective of the study is to understand signals that regulate the development of ABC and
autoreactive PC in lupus nephritis patients in hopes of identifying new therapeutic targets. Preliminary data
suggest that ABC develop after B cell activation in the presence of interferon-gamma (IFN-γ) and interleukin
21. ABC are hyper-responsive to type III interferon (IFN-λ). PC differentiation can be promoted by IFN-λ in
healthy B cells. In this application, Aim 1 will determine how interferon lambda (IFN-λ) promotes ABC
differentiation to PC by examining epigenetic and gene expression changes in B cells treated with IFN-λ. Aim
2 will define the relationships between ABC and their cellular neighbors in the renal microenvironment. In
particular, the developmental relationship between ABC and other B cells in the kidneys of lupus nephritis
patients will be examined using transcriptomic approaches. A gene expression map of the cellular neighbors
of ABC and PC in the lupus nephritis renal microenvironment will be created using spatial transcriptomic
analysis. This will identify factors that may be promoting the development of autoimmunity in lupus nephritis.
This project will allow Dr. Jennifer Barnas, MD, PhD to develop her skill set in molecular techniques such
epigenomics, spatial and single cell transcriptomics and biostatistical anlaysis of these large data sets under the
mentorship of Dr. Jennifer Anolik, an expert in lupus B cell biology, Dr. Martha Susiarjo, an expert in epigenetic
regulation of disease, and Dr. Andrew McDavid, a computational biologist with extensive experience in single-
cell analysis of immune cells. Dr. Barnas will use these techniques to develop an independent research program
at University of Rochester and apply for NIH R01 funding to study B cell activation pathways and PC development
in autoimmune disease. This work will inform the origin of ABCs and establish whether pathways revealed by in
vitro studies are functioning in clinically relevant tissue samples.

## Key facts

- **NIH application ID:** 10869898
- **Project number:** 5K08AI168450-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Jennifer Lynn Barnas
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $192,240
- **Award type:** 5
- **Project period:** 2023-06-16 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869898

## Citation

> US National Institutes of Health, RePORTER application 10869898, Autoimmunity-Associated B Cells in Lupus Nephritis (5K08AI168450-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869898. Licensed CC0.

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