# Microbe-driven Development of GALT

> **NIH NIH R01** · LOYOLA UNIVERSITY CHICAGO · 2021 · $461,588

## Abstract

Abstract
Microbiota are required for the development of secondary lymphoid tissues, including gut-
associated lymphoid tissues (GALT). Interactions between GALT and the microbiota are
especially important in rabbits, as B cells proliferate and mutate their V(D)J genes in response
to select commensal bacteria. Further, VHa B cells, identified because they utilize VH1, are
selectively expanded in GALT as a result of specific commensal bacteria. In contrast, other B
cells, designated VHn, do not expand in GALT. VHa and VHn B cells differ primarily in the
external surface of framework regions (FR) 1 and 3, and we propose that VHa-specific amino
acids on the external surfaces of FR1 and FR3 form a binding motif that together with TLR
signaling through MyD88, mediates selective expansion of VHa B cells by binding bacterial cell
surface molecules. We hypothesize that this innate-like, non-antigen-specific stimulation
through the B cell receptor (BCR) facilitates selective expansion of VHa B cells and
diversification of the primary Ab repertoire. In Aim 1, we will test this hypothesis by identifying
bacteria in GALT that selectively bind to and activate VHa but not VHn B cells. Aim 2 will test if
the identified bacteria specifically drive expansion of VHa B cells in vivo; and in Aim 3, we will
explore the mechanism by which the bacteria stimulate VHa B cells. The results will elucidate a
new mechanism by which bacteria interact with B cells to promote development of the immune
system.

## Key facts

- **NIH application ID:** 10149917
- **Project number:** 5R01AI140132-04
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Katherine L. Knight
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $461,588
- **Award type:** 5
- **Project period:** 2018-05-25 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149917

## Citation

> US National Institutes of Health, RePORTER application 10149917, Microbe-driven Development of GALT (5R01AI140132-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10149917. Licensed CC0.

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