Investigating the Effect of Antibody-Mediated Feedback on Ongoing Germinal Center Responses

Author

Alexandru Barbulescu

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

Recommended Citation

Barbulescu, Alexandru, "Investigating the Effect of Antibody-Mediated Feedback on Ongoing Germinal Center Responses" (2023). Student Theses and Dissertations. 750.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/750