# Development of Intestinal Polyreactive IgA B Cells

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $498,426

## Abstract

A large fraction of the intestinal commensal microbiota is coated with IgA antibodies in homeostatic conditions,
but the strategy and the mechanisms deployed to confront the immense diversity of bacterial antigens have
remained elusive. Converging studies indicate that homeostatic IgA responses employ a highly polyreactive
repertoire to bind broad but distinct subsets of microbiota. These antibody responses develop in the presence
of limited T cell help, with low rate of somatic mutations and little affinity maturation. This new perspective
contrasts with the classical paradigm of T cell-dependent, high-affinity antibody responses elicited by mucosal
pathobionts, pathogens and vaccines, and provides a simple immunological solution to the challenge of
microbiota antigenic complexity. It also raises several fundamental issues, including how polyreactive
specificities are generated and selected in the IgA repertoire, and how they coexist or overlap with other
immune responses during homeostasis and disease. This project addresses these issues by (i) generating
polyreactive IgA knock-in mice using CRISPR/Cas9 technology to (ii) understand the development and
differentiation of polyreactive IgA precursor B cells and (iii) to study the function of polyreactive IgA at the
clonal level in the context of intestinal and extraintestinal challenges. These studies will clarify a major gap in
our understanding of polyreactive B cell repertoires, address a challenge to existing dogmas of antibody
specificity and tolerance, and develop new knowledge, concepts and tools for a better understanding of
intestinal immunity, inflammatory bowel diseases and oral vaccines.

## Key facts

- **NIH application ID:** 9850505
- **Project number:** 5R01AI144094-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** ALBERT S. BENDELAC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $498,426
- **Award type:** 5
- **Project period:** 2019-01-17 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850505

## Citation

> US National Institutes of Health, RePORTER application 9850505, Development of Intestinal Polyreactive IgA B Cells (5R01AI144094-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9850505. Licensed CC0.

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