SEX hormones that control antibody class switching to IGG
Active Project Grant Awarded Last action
- Award ID
- F31AI188593
- Recipient
-
President And Fellows Of Harvard College UEI JDLVAVGYJQ21 Part of Harvard College President & Fellows Of
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $76,560
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 3% complete
- Originally
- Place of performance
- Boston, MA 02115, USA
Award details come from USAspending.gov.
Description
- Abstract
- 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 B cell CSR, a core immune reaction that forms a basis of humoral immunity.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $38,280 | |
| Amendment | $0 | |
| Original award | $38,280 |
Quick answers
Who received award F31AI188593?
F31AI188593 was awarded to President And Fellows Of Harvard College by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on October 7, 2026.
How much is award F31AI188593 worth?
$76,560 has been obligated on F31AI188593.
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