Advisory Committee Chair
Andre Ballesteros-Tato
Advisory Committee Members
Laurie Harrington
Craig Maynard
Troy Randall
Hubert Tse
Amy Weinmann
Document Type
Dissertation
Date of Award
2023
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
T follicular helper (Tfh) cells constitute a distinct subset of CD4 T cells that reside within B cell follicles, playing an indispensable role in orchestrating the Germinal Center (GC) response. In response to polarizing environments, such as Influenza A virus infection (IAV), Tfh cells secrete effector cytokines, including IFN-γ and IL-4. Nevertheless, the specific functions of cytokine-producing Tfh cell subsets, beyond their involvement in driving class switch recombination (CSR), remain largely unexplored. Here, we demonstrate that, following IAV infection, Tfh cell cytokine production undergoes a dynamic shift, transitioning from early IFN-γ dominance to later predominance of IL-4. The initial IFN-γ production by Tfh cells influences the GC B cell response, skews cells towards memory B (Bmem) cell differentiation, and thus contributes to the development of lung-memory B cells (lung-BRMs), a specific Bmem population that takes residence in the lungs and rapidly differentiate into antibody-secreting cells (ASC) upon antigen re-encounter. This mechanism accelerates the secondary antibody response in the event of antigen re-exposure. Mechanistically, IFN-γ signaling, sourced from Tfh cells, acts intrinsically on GC B cells, upregulating T-bet and facilitating the generation of CXCR3+ precursor memory B cells (preMems), which serve as precursors to lung-BRMs. Consequently, in the absence of Tfh cells producing IFN-γ, CXCR3+ pre-Mem B cell generation in GC B cells is hindered, ultimately obstructing lung-BRM cell differentiation. Our findings propose a model wherein transient changes in Tfh cell cytokine profiles dynamically influence GC fate decisions during influenza infection, providing novel insights into the determinants of the GC response outcome.
Recommended Citation
Arroyo-Diaz, Nicole Michelle, "Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses" (2023). All ETDs from UAB. 3475.
https://digitalcommons.library.uab.edu/etd-collection/3475