# T-bet expressing B cells in autoimmunity

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $245,688

## Abstract

Systemic Lupus Erythematosus (SLE) is a potentially fatal autoimmune disease characterized by the
production of pathogenic autoantibodies that recognize nucleic acid containing antigens. These antibodies
form immune complexes that promote tissue damage in multiple organs and perpetuate a systemic
inflammatory environment. The majority of current therapies for SLE involve non-specific immunosuppression
and have undesirable side effects. Thus there is an urgent need for more targeted therapies. Recent studies
have demonstrated that autoreactive B cells have unique requirements for their activation, participation in
germinal centers, and differentiation into antibody secreting plasma cells compared to B cells reactive with
foreign antigens. Understanding the consequences of these differential signals may reveal new therapeutic
strategies to prevent autoimmune responses while maintaining the ability to respond to infection. The
transcription factor T-bet is a) upregulated by stimuli that are uniquely required for autoreactive B cell
responses and b) increased in germinal center B cells and ABCs in mouse lupus models and in DN2 cells from
SLE patients. ABCs and DN2s are B cell subsets that accumulate in lupus and differentiate efficiently into
plasma cells that secrete elevated levels of autoantibodies. However, the degree to which T-bet expressing B
cells contribute to the production of pathogenic autoantibodies is unclear, as prior results have been
contradictory. A better understanding of this is necessary in order to support these cells as a therapeutic target
for lupus. We posit that T-bet expression is a marker for cells that give rise to autoantibodies in lupus models,
even if it is not itself absolutely required for autoantibody production. We will test this hypothesis by 1) using a
fate mapping strategy to determine the contribution of cells that express, or once expressed, T-bet to the
accumulation of autoreactive plasma cells, and 2) preventing T-bet expressing B cells from differentiating into
plasma cells in a lupus model. Successful completion of these studies will highlight T-bet expressing B cells or
stimuli that induce them as potential therapeutic targets for SLE. The methods developed here to delete
genes specifically in T-bet expressing B cells will also be valuable for future mechanistic studies involving
these cells both in autoimmune disease and during immune response to infections.

## Key facts

- **NIH application ID:** 10231925
- **Project number:** 1R21AI161307-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Anne B Satterthwaite
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $245,688
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231925

## Citation

> US National Institutes of Health, RePORTER application 10231925, T-bet expressing B cells in autoimmunity (1R21AI161307-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10231925. Licensed CC0.

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