# Humoral Immunity by Anergic B cells

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $510,564

## Abstract

PROJECT SUMMARY
 Not all autoreactive B cells are censored by central tolerance during their development. Thus,
mechanisms of B cell anergy are essential for the functional silencing of autoreactive B cells that exist in the
periphery in both humans and mice. However, it remains unclear why this poorly defined process of
immunological tolerance allows for the temporary retention of autoreactive B cells in the periphery given that,
under certain genetic and environmental settings, these cells can contribute to autoimmunity. Indeed, anergic
B cells can be released from their functionally inert state but requires unique circumstances (e.g., strong TLR
stimulus and highly multimerized antigen), which could presumably occur during an uncontrolled infection. As
such, we propose that autoreactive anergic B cells may serve as a reserve population able to respond to
pathogens not contained by an initial immune response and particularly for pathogens that aim to evade the
immune response through molecular mimicry of self-antigens. Accordingly, work from our lab has recently
evaluated if autoreactive B cells that are normally silenced by immune tolerance can contribute to a protective
cross-reactive antibody response. To accomplish this we used both autoimmune prone B6.Sle123 mice and
wild-type mice treated with pristane, a treatment characterized to impair tolerance and promote autoantibody
production. These mice were immunized with HIV envelope protein (Env) and immune sera was found to
neutralize tier 2 genetic subtypes of clinically relevant HIV-1, a pathogen proposed to exploit immune tolerance
in order to evade the immune response. Furthermore, from these mice we isolated Env-specific neutralizing
monoclonal antibodies that also recognize the H2A histone protein. Thus, the goal of this proposal is to use
mouse and humanized mouse models to identify the nature and mechanisms that facilitate this antibody
response by peripheral autoreactive B cells and to establish conditions that experimentally breach tolerance
and promote cross-reactive autoantibody responses by anergic B cells.

## Key facts

- **NIH application ID:** 10460932
- **Project number:** 5R01AI136534-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Raul Martin Torres
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $510,564
- **Award type:** 5
- **Project period:** 2018-07-03 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460932

## Citation

> US National Institutes of Health, RePORTER application 10460932, Humoral Immunity by Anergic B cells (5R01AI136534-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460932. Licensed CC0.

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