Evaluating the anatomical localization of SARS-CoV-2-specific plasma cells

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020, combined efforts have been employed to understand the mechanisms of SARS-CoV-2 infection. The respiratory virus causes COVID-19 by binding via receptors in human airways with a spike protein. Neutralization of SARS-CoV-2 is dominated by an immunoglobulin A (IgA) antibody response in human saliva samples. Preliminary work by our lab has found an increased amount of IgA specific to SARS-CoV-2 proteins in acute and recovering patients compared to negative controls. However, the origin of SARS-CoV-2 antibodies and their distribution in primary immune responses remain undetermined. As we explore pathogens such as SARS-CoV-2, understanding the role of antibodies in immune protection and response regulation is crucial. Recent studies suggest that specific immune cells, called IgA-secreting plasma cells, migrate between tissues during health and disease. Despite these advances, cellular migration mechanisms in SARS-CoV-2 also remain unclear. Therefore, we hypothesize that IgA-producing plasma cells distribute throughout the body to mediate host defense during SARS-CoV-2 infection. We will investigate the origin of IgA antibody-secreting cells (ASCs) and where they reside using a knock-in mouse model for humanized ACE2. We will characterize immune cells within tissues in the respiratory system and lymphoid organs using fluorescence-based imaging techniques We will also characterize the immune cell populations using the same mouse model to determine the ASC migration into effector tissues after infection resolves. Understanding additional mechanics of antiviral IgA provides vital knowledge to monitor seroprevalence in communities and to inform better vaccine design against COVID-19.