Taru Dutt Poster 2025
Dr Taru Dutt
Colorado State University, USA
Lung-Resident B Cells in Tuberculosis: Unravelling Their Role in Local Immunity and Vaccine Development
Poster Abstract
Tuberculosis (TB) remains a leading cause of infectious disease mortality, underscoring the urgent need for improved vaccines. While TB vaccine strategies have historically focused on T cell-mediated immunity, emerging evidence suggests that B cells—particularly lung-resident B cells—play a pivotal role in shaping local immune responses at the site of infection. Unlike circulating B cells, these tissue-resident populations could contribute directly to immune surveillance, antigen presentation, and antibody production. However, their role in TB immunity remains largely unexplored.
Our research demonstrates that exposure to non-tuberculous mycobacteria through drinking water leads to the formation of ectopic germinal centers (eGCs) in the lungs. These structures act as specialized immune hubs where follicular dendritic cells present antigens to B cells, facilitating selection and affinity maturation. Using this mouse model, we found that eGCs emerge between 60 and 120 days post-Mycobacterium tuberculosis (Mtb) infection (DPI), with early B and T cell aggregates appearing by 60 DPI and fully developed eGCs forming by 120 DPI.
Longitudinal analysis of pulmonary eGCs revealed a significant enrichment of affinity-matured, memory, and marginal zone B cells, which correlated with a reduced Mtb burden in the lungs. This finding underscores the active role of B cells in shaping the immune response within eGCs. Additionally, ligand-receptor interaction analysis identified robust signaling between B cell-expressing lymphotoxin ⍺/β and its receptors Tnfrsf1a, Tnfrsf1b, and Tnf-Tnfrsf14 on dendritic and stromal cells, suggesting that B cells are central to orchestrating eGC formation and function.
Despite these findings, fundamental questions remain regarding the mechanisms by which lung-resident B cells initiate and sustain eGC development, their antigen specificity, and their precise contribution to bacterial clearance. Our research aims to unravel these mechanisms, offering vital insights into B cell-driven immunity in TB and advancing next-generation vaccines that harness localized humoral immunity for enhanced and long-lasting protection.
Biography
Dr. Taru S. Dutt is a systems immunologist specializing in B cell immunity and tuberculosis (TB). Her research focuses on understanding how lung-resident B cells shape TB disease outcomes, uncovering their role in immune regulation, antibody production, and ectopic germinal center formation. By integrating traditional immunology with advanced computational tools, including single-cell RNA sequencing and high-dimensional data analysis, Dr. Dutt aims to identify novel therapeutic targets. Her work paves the way for developing targeted vaccines and immunotherapies that harness localized lung immunity against TB.
