The Influence Of The Lung Virome On Pulmonary B Cells

Abstract The human microbiome is a complex and diverse environment that is implicated in human health and disease. Major locations that host a microbiome include the gut, respiratory system, and the urogenital tracts. While there have been steady advances of the effect of our commensal flora in regions such as the gut microbiome, the impact of the pulmonary microbiome, specifically the viral arm of the microbiome (virome), remains unclear and under-researched. Recent studies have shown that pulmonary viruses can influence disease susceptibility to the benefit, or detriment, to the host. Despite increasing evidence that the lung virome influences human health through the immune system, the direct effects on the host immune system remain unclear. We hypothesize that the chronic presence of the lung virome influences the pulmonary B cell repertoire. The constant exposure to pulmonary virus can generate a unique B cell repertoire independent of peripheral B cells that is tailored specifically towards pulmonary viruses. To address this hypothesis, we have utilized a single-cell B cell culture system to amplify human lung-derived memory B cells (MBCs) from limited human donor samples. By analyzing these MBCs at the genetic level by RNA sequencing and protein level by antigen affinity from secreted antibodies, we can begin to understand the impact of the lung virome on the pulmonary B cell repertoire.