# Effect of B-cell depletion on vaginal microbiota and mucosal immunity

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

## Abstract

PROJECT SUMMARY
The vaginal microbiome plays a significant role in reproductive health outcomes, influencing a woman’s chances
of pregnancy implantation, miscarriage, low birth weight, preterm delivery, and acquisition of sexually transmitted
infections. While many studies have shown that changes in the female genital tract (FGT) microbiota drive
changes in the mucosal immune environment, there are few studies that have explored the alternate possibility:
that changes in host mucosal immunity determine the composition of the vaginal microbial community. We have
described a Lactobacillus-deficient, inflammatory vaginitis in women treated with rituximab, an anti-CD20
antibody which leads to systemic B-cell depletion. This observation led us to hypothesize that B-cells and
vaginal fluid antibodies regulate the composition of the vaginal microbiota, controlling levels of
pathobionts such as E. coli and Group B streptococcus and facilitating Lactobacillus dominance.
Although associations between B-cells, antibodies and microbiota have been described in the gut, this is an
unexplored area in the female genital tract. Our proposed project is novel in both exploring the role of B-cells
and antibodies in regulation of vaginal microbiota, but also in using clinical rituximab treatment as an in vivo
experimental model. This exploratory grant has potential to identify highly significant biologic mechanisms for
regulation of FGT microbiota and mucosal inflammation, both of which are associated with adverse reproductive
health outcomes. To test our hypothesis, we propose an observational study comparing women treated with
rituximab to healthy controls to identify the role of B-cells in determining the composition of the vaginal microbiota.
In Aim 1 we will compare the vaginal microbiota, cervical immune cells, vaginal fluid immunoglobulins and
soluble markers of inflammation between 40 women being treated with rituximab to 40 healthy controls. We will
also compare these markers between women being treated with rituximab with inflammatory vaginitis and those
without. In Aim 2, we will assess the causal relationship with B-cell depletion by comparing changes in our
measured analytes over time in women who are 1) starting, 2) stopping and 3) stable on treatment with rituximab
(n = 10 in each group). Our local vaginal measurements of immune cell populations and soluble markers will be
compared with systemic measurements of B-cell numbers and IgG levels. Using rituximab treatment as an in
vivo experimental model will provide a novel opportunity to examine the role of systemic immunity in regulating
the vaginal microbiota and mucosal immune responses, which will lead to broader understanding of both vaginal
and systemic mucosal immunity.

## Key facts

- **NIH application ID:** 10374759
- **Project number:** 5R21AI156038-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Caroline M Mitchell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $252,000
- **Award type:** 5
- **Project period:** 2021-03-19 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374759

## Citation

> US National Institutes of Health, RePORTER application 10374759, Effect of B-cell depletion on vaginal microbiota and mucosal immunity (5R21AI156038-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10374759. Licensed CC0.

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