Investigation of potent B cell responses to particulate antigens 3200

Abstract Description Autoreactivity is a normal feature of the mature B cell repertoire. Therefore, B cells must discriminate self from foreign antigens in order to prevent autoimmunity. The nature of the antigen likely provides important cues to the responding B cell, determining whether its fate will be tolerance or differentiation into an antibody-secreting cell. We use liposomal particles of viral size decorated with the model antigen hen egg lysozyme (HEL) to test how antigen-specific B cells respond to particulate antigen display. In contrast to soluble antigen, particulate antigen induces signal amplification downstream of the BCR by evading Lyn-dependent inhibitory tone. Particulate and soluble antigen induce divergent nuclear translocation of the key transcription factors NFAT and NF-kB, resulting in distinct functional outputs. Notably, particulate antigen can mimic T cell help to support differentiation into bona fide antibody-secreting cells. Finally, particulate-antigen stimulated B cells can serve as antigen-presenting cells to recruit T cells. Our studies uncover a molecular basis for highly sensitive B cell responses to particulate antigen display, provide clues as to how B cells decipher foreign versus self antigens, and serve as a platform for understanding how to design vaccines that elicit humoral and cellular responses. Funding Sources R01AI155653, R01AI148487, R01AR069520, NIH Training Grants T32 AI007334 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)