Student Theses and Dissertations

Date of Award

2023

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Victora Laboratory

Abstract

Antibodies play a crucial role in protection against a wide range of pathogens. As such,the goal of most vaccinations is to induce immune memory in the form of long-lasting,high-affinity serum antibody titers, which requires the participation of B cells in the germinal center (GC) response.It is well-established that pre-existing antibodies can influence the outcome of future humoral responses; however, whether antibody from an ongoing response can feedback onto contemporaneous GCs to influence B cell clonal selection and affinity maturation in real-time remains poorly understood.Here we present a genetic mouse tool to interrogate the effect of antibody-mediated feedback on ongoing GC res with B cell receptor specificities to non-overlapping epitopes on the same antigen, allowing us to distinguish between epitope-specific and epitope-non-specific effects of secreted antibody.In addition, we have genetically engineeredaBlimp-1-DTRmousethat allows for temporally controlled ablation of plasma cells and,therefore,depletion of antibody titers.Combining these two models has revealed that high levels of antibody produced during B cell responses can modulate interclonal selection in the GC by suppressing GC B cells that bind the same epitopes.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Download

Included in

Life Sciences Commons

Share

COinS