Stefano Travaglino
BME PhD Proposal Presentation

Date: 2024-01-17
Time: 8:45-9:45 AM
Location / Meeting Link: Whitaker 2110 and https://teams.microsoft.com/l/meetup-join/19%3ameeting_MDhhNDBkMmItODU0OC00MzIzLWJmYjAtMjcwYWQxOWQ2YjM4%40thread.v2/0?context=%7b%22Tid%22%3a%22482198bb-ae7b-4b25-8b7a-6d7f32faa083%22%2c%22Oid%22%3a%22422de191-41e8-4427-8327-22252bc02976%22%7d

Committee Members:
Dr. Cheng Zhu (Advisor); Dr. Ankur Singh; Dr. Jürgen Wienands; Dr. Gabriel Kwong; Dr. Leslie Chan


Title: Mechanobiology of B cell immunoreceptors

Abstract:
B cells interact with follicular dendritic cells (FDCs), internalizing antigens through B cell receptors (BCRs), which are then presented on MHCs for recognition by T cells. Naïve B cells that interact with FDCs initially express two BCR isotypes, IgM and IgD, but their distinct roles remain unclear. Upon successful BCR binding, antigen extraction, and presentation on MHCs, T cells that successfully recognize the antigen pMHCs express CD40L, which in turn interacts with CD40 on B cells to communicate recognition of the same antigen. This thesis aims to dissect the role of mechanotransduction in receptor-ligand interactions at the B cell immune synapse and in the resulting B cell immune responses. The first primary objective is to investigate the mechanics of CD40-CD40L interactions, crucial in B cell co-stimulation and implicated in immune deficiencies like X-linked Hyper IgM syndrome (X-HIgM). The second is to unravel the mechanobiology of BCR-antigen interactions across different BCR isotypes and antigen valency, assessing the impact of mechanical forces on BCR binding and signaling. The mechanobiology of CD40 and BCR will be studied using highly sensitive, single molecule, single cell, and high throughput biomechanical assays. This research aims to provide significant insights into the biophysical aspects of B cell immune receptor interactions and their implications for the adaptive immune response.