# TLR-dependent B cells in Lupus

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $241,875

## Abstract

Project Summary
A major deficiency in understanding the role of B cell in lupus and in devising rational therapies targeting B
cells is the gap in knowledge about the generation and fate of autoantibody-producing B cells. Previous
studies have established that endosomal TLR signaling in B cells is central to the production of autoantibodies
in lupus. This project seeks to apply this finding toward developing a new animal model of lupus that will make
it possible to follow the developing endosomal TLR-dependent and autoantibody-producing B cells and their
differentiation and progression over a long period. To accomplish this, we propose to develop a model in
which B cells from lupus mice are transferred into lupus mice deficient in endosomal TLR signaling because of
the 3d mutation. 3d is a function-ablating mutation in UNC93B1, a transport protein essential for endosomal
TLRs. Initial results involving the transfer of B6-lpr IgHa CD45.1 B cells into B6-lpr 3d IgHb CD45.2 mice
demonstrated a marked production of IgM and IgG2a from donor B cells as well as persistence of a small
cohort of transferred B cells that over several weeks acquired phenotypic characteristics of memory B cells.
For this project, two aims are proposed. Aim 1 will develop this model for studying eTLR-dependent B cell
activation and autoAb production, and Aim 2 will define factors affecting eTLR-dependent B cell responses.
Successful development of this system will make it possible to examine the development and long-term fate of
autoantibody-producing B cells.

## Key facts

- **NIH application ID:** 9832168
- **Project number:** 5R21AI138512-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** DWIGHT H KONO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $241,875
- **Award type:** 5
- **Project period:** 2018-12-06 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832168

## Citation

> US National Institutes of Health, RePORTER application 9832168, TLR-dependent B cells in Lupus (5R21AI138512-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9832168. Licensed CC0.

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