# Sex hormones that control antibody class switching to IgG

> **NIH AI F31** · HARVARD MEDICAL SCHOOL · 2026 · $38,280

## Abstract

Project Summary
As a PhD candidate in the Lingwood laboratory at the Ragon institute of Mass General, MIT and Harvard, I
propose to mechanistically define how B cell class switch recombination (CSR), a core immune reaction
underscoring all humoral immunity (e.g. IgM -> IgG), is modulated by sex differences in hormones and circulating
cytokines. Adaptive immunity, including the generation of IgG, is often elevated in females, however mechanistic
reasons are lacking. In preliminary data, I find that the circulating levels of APRIL, a cytokine that stimulates CSR
independently of conventional T cell help, is higher in female as compared in male mice. This correlates with
heightened APRIL signaling in human females. Antibody responses to T cell/thymus-independent (TI) antigens
(non-protein pathogen features such as bacterial glycan polymers and lipids) are dependent on ligation of the
APRIL receptor TACI and I demonstrate that IgG switching within this pathway is correspondingly higher in
females. The sex differences in both APRIL and IgG switching can be reversed by male gonadectomy (GDX) to
remove circulating testosterone. I will now test the central hypothesis that test the central hypothesis that
testosterone suppresses APRIL, lowering the class switched IgG in response. In Aim 1 I will apply
orthogonal methods to experimentally alter circulating levels of APRIL and/or testosterone in mice to assess
hormone feedback on APRIL and control over IgG switching within the TACI-dependent TI-response pathway. In
Aim 2, I will deploy a model of bone marrow chimerism I have developed to stably engraft the host lymphoid
organs with sex-mismatched CD45+ leukocytes (macrophages, granulocytes, monocytes and T and B
lymphocytes). This system will experimentally distinguish cell intrinsic (e.g. XX vs XY) from environmental (testis
vs ovary) contributions to sex differences in TI antibody output. Overall, this proposal aims to rigorously define a
mechanism for sex-based control over

## Key facts

- **NIH application ID:** 11309765
- **Project number:** 1F31AI188593-01A1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Lindsey  Adams
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $38,280
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2029-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11309765

## Citation

> US National Institutes of Health, RePORTER application 11309765, Sex hormones that control antibody class switching to IgG (1F31AI188593-01A1). Retrieved via AI Analytics 2026-07-11 from https://api.ai-analytics.org/grant/nih/11309765. Licensed CC0.

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