# Effects of neonatal microbial exposure on anti-polysaccharide B cell development

> **NIH NIH U01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $371,250

## Abstract

ABSTRACT
Innate-like B cell-derived natural antibodies (NAbs) against T-independent polysaccharide (PS) and
phospholipid epitopes are universally present in mammals and serve important roles in the protection against
many bacterial pathogens. However robust antibody responses against PS antigens following infection or
immunization are absent in neonates. We previously showed that neonatal exposure to PS and phospholipid
antigens by immunization or natural colonization with the microbiota, influences the clonal distribution of
antigen-specific innate-like B cells leading to quantitative increases in natural antibody (Nab) levels. These
effects impact adult susceptibility to infection, and immune-responsiveness to allergens and auto antigens
bearing similar B cell epitopes. Although the microbiota impacts the development of other lymphoid lineages its
role in the development of the adult innate-like B cell and NAb repertoires is largely unexplored. Our
hypothesis is that in addition to the well-described selection processes that occur during B cell development,
the accessibility to autologous antigens and exogenous commensal-derived epitopes combine during neonatal
development to shape the natural repertoire. The goal of these proposed studies is to elucidate mechanisms of
exogenous antigen-directed development of the innate-like B cell repertoire using three model B cell antigen-
specificities that represent epitopes for relevant pathogenic and commensal organisms with a spectrum of auto
antigenic potential: phosphorylcholine (PC), N-acetyl-D-glucosamine (GlcNAc), and dextran (DEX). In Aim 1 of
these studies wild-type gnotobiotic mice will be colonized with defined microbiota to assess the contribution of
exogenous antigen signaling on clonal B cell development and formation of the NAb repertoire. Bone marrow
chimera systems, composed of antigen-specific immunoglobulin (Ig) heavy chain-transgenic mouse strains,
and lineage tracking will enable assessment of endogenous and exogenous antigen signaling on B lymphocyte
selection and receptor editing processes. In Aim 2 we will analyze the frequency, cell surface phenotype,
subset and isotype distribution as well as immunoglobulin gene usage of human B cells specific for these
antigens. Examination of B cells isolated from cord blood, tonsils/adenoids, and peripheral blood B cells of
donors of different ages will provide novel insight into the role of antigen experience in the formation of innate-
like B cell repertoire diversity within and across individuals. Antigen-specific Ig genes will be cloned and
expressed as recombinant antibody to determine effects of antigen-driven maturation on functions of these
human antibodies. Collectively, these studies will define the microbial influences on NAb development in mice,
determine developmental kinetics of human NAb development, and compare and contrast the NAb repertoire
development between both species. This insight into the human infant responses to inf...

## Key facts

- **NIH application ID:** 9980265
- **Project number:** 5U01AI100005-09
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** John Franklin Kearney
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2012-03-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980265

## Citation

> US National Institutes of Health, RePORTER application 9980265, Effects of neonatal microbial exposure on anti-polysaccharide B cell development (5U01AI100005-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980265. Licensed CC0.

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