# Role of Memory IgG B Cells in the Development of Tolerance in Food Allergy

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $252,000

## Abstract

Only a subset of patients with IgE-mediated food allergy develop clinical tolerance after oral
immunotherapy (OIT), which has been attributed to the development of protective, functionally suppressive
antibodies. However, those who lose tolerance are often seen to have an early transient increase in allergen-
specific IgE. Previously, we have described the induction of allergen-specific memory B cells early in OIT, and
these specific IgG B cells could serve as a reservoir of IgE memory via sequential class-switching. Therefore,
the relative contribution of specific IgG B cells giving rise to protective IgG or IgA antibodies versus pathogenic
IgE is critical to the development of immunological tolerance in OIT. Understanding the contributions of that B
cell fate decision could lead to the development of new therapeutic modalities for allergic diseases.
 In OIT, we recently published that suppression of basophil sensitivity is a biomarker of tolerance.
Functional suppression of basophils and not bulk levels of allergen-specific IgG is correlated with tolerance,
suggesting that the antibody repertoire induced by OIT may be highly relevant to the development of tolerance.
We have developed a highly specific fluorescent multimer to identify and characterize allergen-specific B cells
in peanut OIT in order to define the clonal contributions of these B cells. Using these tools, we propose to track
clonal evolution from the memory IgG B cells induced by OIT to the post-serum effector antibodies to explain
how antibody evolution from specific IgG B cells influences clinical outcomes in OIT.
 Based on these findings, we hypothesize that allergen-specific memory IgG B cells can give rise to
either protective or pathogenic antibodies that determine long-lived tolerance after OIT. Our approach
combines the isolation of antigen-specific B cells for single-cell BCR sequencing, BCR repertoire analysis, and
serum proteomics to dissect the clonality of serum antibodies to the peanut allergen, Ara h 2, over the course
of OIT. We are uniquely positioned to conduct this study in that we have both serum and BCR repertoires from
previously characterized OIT-treated patients. We will address our hypothesis in the following specific aims: (1)
Evaluate the development of protective, functionally suppressive allergen-specific IgG in sustained tolerance
after OIT; and (2) Evaluate the role of sequential switching in the loss of tolerance after OIT.
 We anticipate that the proposed studies will elucidate the connection between long-lasting clinical
efficacy of OIT on a clonal level with protective and pathogenic antibodies, highlighting the critical role of
memory allergen-specific IgG B cells and leading to new strategies for the treatment of food allergies. The
development of techniques to track antigen-specific B cell fate, using BCR sequencing, proteomics and
recombinant antibodies, will provide a powerful platform to further refine our understanding of how humoral
immun...

## Key facts

- **NIH application ID:** 10377446
- **Project number:** 5R21AI159732-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Sarita U Patil
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $252,000
- **Award type:** 5
- **Project period:** 2021-03-24 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377446

## Citation

> US National Institutes of Health, RePORTER application 10377446, Role of Memory IgG B Cells in the Development of Tolerance in Food Allergy (5R21AI159732-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10377446. Licensed CC0.

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