Improving protective humoral immunity at mucosal sites: the regulation and maintenance of IgA-producing plasma cells in the gut 3400

Abstract Description In the gut, IgA stands out as the predominant antibody produced by plasma cells (PCs), significantly contributing to proactive protection against various pathogens, including viruses. PCs can be broadly classified into short-lived (SLPCs) and long-lived (LLPCs) categories, with the latter capable of providing humoral immunity for decades, yet remaining poorly characterized. There is a lack of understanding of how the longevity of this humoral immune arm is supported and spatially localized. This project aims to address this gap by employing a plasma cell-specific Cre mouse model to temporally track PCs during homeostasis and murine norovirus (MNV), an enteric viral infection. We performed the multimodal single cell sequencing and immunofluorescence imaging on PCs from a novel lineage tracing mouse and learned about differences in transcriptional program of LLPCs and their supportive environment. We are using this information to further elucidate how intrinsic and extrinsic LLPC characteristics in IgA LLPCs promote their survival in intestinal niches compared to SLPCs, particularly related to BCR signaling, pro-survival, chemotaxis and integrins. These discoveries promise to enhance understanding of molecular signatures essential for PC longevity, potentially leading to the development of longer-lasting IgA responses at mucosal sites. Funding Sources HHMI Gilliam Fellowship; NIH 5R21AI37752 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)