Defining the transcriptional signature and heterogeneity of lung resident memory B cells

Abstract

Abstract Lung resident memory cells have been shown to drive protection against viruses and bacteria, and recently resident memory B cells (BRM) have been also recognized in humans and animal models as critical immune mediators of protection from pathogens. Compared to naïve B cells, circulating influenza-specific memory B cells harbor a unique epigenetic and transcriptional landscape. Although lung-resident memory T cells have distinct molecular programming, it is not known if lung BRM are similarly programmed or distinct. Recent work has defined the emergence and requirement for T cell help in the formation of BRM, suggesting a distinct set of signals are required to promote lung residency compared to circulating memory. Here we investigated the unique programming of lung BRM and plasma cells to determine how their unique transcriptional, metabolic, and epigenetic properties. We used single-cell RNA sequencing (sc-RNA-seq) on sorted lung resident and mediastinal LN (mLN) memory B cells and antibody secreting cells from influenza-infected C57BL/6 mice 35 days post-infection. As a comparison, circulating naïve B cells were also sorted. Here, we investigated BRM heterogeneity and transcriptional programming in the lung tissue. Comparisons to tissue resident memory T cells define metabolic characteristics that promote survival in the lung microenvironment. These data defined the BRM molecular properties compared to circulating B cells and their unique relationship to plasma cells in the lung. Supported by grant 5R01AI148471-02 from NIH