# B Lymphocytes in Autoimmune Disease

> **NIH VA I01** · ST. LOUIS VA MEDICAL CENTER · 2024 · —

## Abstract

Rheumatoid arthritis (RA) results from a complex cascade of events that breaks immune
tolerance and culminates in the destruction of synovial tissue. Both genetic and environmental
factors contribute to disease. B lymphocytes (B cells) play a critical role, producing the
autoantibodies that trigger arthritis. The Kendall lab works toward understanding B cells that
support arthritis development. We originally used mice deficient in the B cell signaling protein
Bruton’s tyrosine kinase (BTK) to test its role in the K/BxN model of spontaneous autoimmune
arthritis. The studies indicated significant disease protection, accompanied by loss of
autoantibodies, with relative sparing of total IgG. In the course of this work, we made the new
discovery that BTK also affects the gut microbiome, commensal organisms that are thought to
play an important role in the development of autoimmune diseases, including RA. We found that
specialized immune organs in the gut, called Peyer’s patches, are very small, and that they
make low levels of IgA antibody that does not bind gut bacteria as well as it should. Further,
there is dysregulation of the microbiome that may have a protective effect against autoimmune
arthritis. The hypothesis underlying this proposal is that BTK-mediated signaling
supports mucosal immunity and regulates microbes that influence autoimmunity, to be
tested in Aims which: 1) define the IgA repertoire in Btk-deficient versus –sufficient K/BxN mice,
including features such as selection, clonality and evidence of somatic hypermutation, 2)
determine the cell-specific role of BTK in regulating the microbiome, differentiating between B
cell and myeloid cell functions, and 3) determine whether BTK expression and function in
myeloid and B cells differ in RA patients and controls, and whether IgA binding of commensal
bacteria are altered. This project has direct clinical importance in understanding how aberrant B
cells in autoimmune patients may cause microbiome shifts that modulate disease.

## Key facts

- **NIH application ID:** 10873070
- **Project number:** 5I01BX002882-09
- **Recipient organization:** ST. LOUIS VA MEDICAL CENTER
- **Principal Investigator:** Peggy L Kendall
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873070

## Citation

> US National Institutes of Health, RePORTER application 10873070, B Lymphocytes in Autoimmune Disease (5I01BX002882-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873070. Licensed CC0.

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