# The influence of maternal antibodies on neonatal intestinal immunity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $380,592

## Abstract

How the neonatal immune system avoids inflammatory responses during initial acquisition of the microbiota
remains unclear. Establishing intestinal homeostasis is particularly challenging for neonates because their
immune systems have not fully developed. The goal of this application is to investigate how maternal
antibodies instruct the neonatal immune system to limit T cell responses to newly acquired microbial antigens
in the intestine. This proposal builds on our discovery that mothers generate T cell-independent IgG2b and
IgG3 antibodies reactive with the microbiota and pass these antibodies to their offspring in utero and through
breastmilk. Newborn mice that do not receive any maternal antibodies show increased translocation of
commensal bacteria across the intestinal barrier, mount inappropriate T cell responses against mucosal
antigens, and weigh less for the first few weeks of life. Similar defects are apparent in neonates that only lack
maternal IgG2b and IgG3, demonstrating that these isotypes are required to maintain intestinal homeostasis
early in life. Remarkably, if neonates are experimentally forced to acquire T-dependent IgG2c antibodies
reactive with the microbiota, then they suffer significant mortality and morbidity. Thus, our preliminary results
indicate that the type of antibody acquired by neonates from their mothers can dramatically impact health
during the first weeks of life. This proposal will determine the mechanism by which different IgG isotypes
suppress or enhance responses to the microbiota in neonates. In addition, we will determine whether specific
bacteria drive the immune dysregulation observed in the absence of maternal IgG antibodies or when
inflammatory IgG isotypes are acquired. Overall, the studies described in this proposal will reveal how
microbiota-reactive maternal antibodies regulate neonatal immunity to the microbiota.

## Key facts

- **NIH application ID:** 9986639
- **Project number:** 5R01AI142926-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Gregory M Barton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,592
- **Award type:** 5
- **Project period:** 2018-09-24 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986639

## Citation

> US National Institutes of Health, RePORTER application 9986639, The influence of maternal antibodies on neonatal intestinal immunity (5R01AI142926-03). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9986639. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*