Mechanisms of lung resident memory B cell activation during secondary influenza infection

Abstract

Abstract B cells and the antibodies they produce are essential components of immunity to respiratory viruses, including influenza virus (IAV) and SARS-CoV-2. B cells responding to viral infection can differentiate into antibody secreting cells (ASCs), or resting memory B cells, some of which are tissue-resident (BRM cells). ASCs provide protection by secreting virus-specific antibodies, whereas BRM cells rapidly differentiate into ASCs after secondary infection. We previously published that IAV-specific BRM cells are retained in the lungs and do not recirculate. We now show that many lung-resident BRM cells reside in the airways and can be collected by bronchoalveolar lavage (BAL). BRM cells in the BAL are phenotypically and functionally different than those in the lung tissue and lymph nodes and express markers at various levels that possibly effect function. There is also a distinction in the role of the ASCs between the lungs and the BAL that will secrete certain antibodies at different time points during the IAV challenge. To understand BRM cell homing, differentiation, and function, we are using single cell approaches to define the transcriptional and epigenetic programs of airway-resident BRM cells at resting memory and during the response to IAV challenge. We are also using this technique to identify the changes among the entire immune system during a secondary IAV challenge to gain an understanding of how the entire immune system plays a role in protection. By understanding the programs that regulate BRM placement in the lung and their response to challenge infection, we expect to identify ways to improve vaccines against respiratory viruses and ameliorate B cell-dependent lung pathology in the context of autoimmunity or allergy. Supported by grants from NIH (R01 AI152476)