# Role of Complement Receptor 1 in the Modulation of B Cell Tolerance

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2022 · —

## Abstract

Autoimmune diseases affect more than 2% of the US population, with effects on morbidity and mortality and
associated health care costs that rival those of cancer and heart disease. Both genetic and environmental
factors influence the development of autoimmune diseases, which result from an imbalance between activation
and regulation of the immune system. As our understanding of the immunological mechanisms that drive these
diseases has grown, the impetus has been to develop specific therapies that restore immune tolerance to
disease-associated autoantigens. We recently identified by trans-ancestral mapping a single nucleotide
polymorphism (SNP), rs1876453, located just inside the first intron of the immune-associated complement
receptor 2 (CR2) gene that was enriched in controls rather than lupus cases, suggesting that it had a protective
effect. CR2 is located directly 5’ of complement receptor 1 (CR1) at chromosome 1q32. We found that B cells
from individuals with the protective SNP had increased transcription of the CR1 gene but no changes in CR2
transcriptional levels. We hypothesize that increased transcription of CR1 associated with the protective CR2
SNP results in the active induction of antigen-specific immune tolerance. We will evaluate the mechanism for
this using several immunological and transcriptional approaches and ultimately test whether forced
overexpression of CR1 restores tolerance in a model of systemic lupus erythematosus. We propose that CR1
is a viable target for the early treatment of lupus and other autoimmune diseases during the preclinical phase
in which autoantibodies are present in the absence of symptoms. With rising enlistment into the military of
young minority women who are at increased risk of developing lupus, the future extension of our findings into
tangible interventions will have a substantial impact on veteran health.

## Key facts

- **NIH application ID:** 10316155
- **Project number:** 5I01CX002042-02
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** SUSAN A. BOACKLE
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316155

## Citation

> US National Institutes of Health, RePORTER application 10316155, Role of Complement Receptor 1 in the Modulation of B Cell Tolerance (5I01CX002042-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316155. Licensed CC0.

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