PROJECT SUMMARY Mechanisms of B cell responses to particulate antigens Two biophysical attributes shared by most animal viruses are the display of viral-specific proteins at certain densities on the surface of individual virions and the encapsulation of viral genome inside the virion. A threshold density of viral surface proteins is important to ensure efficient viral infection of host cells. From the perspective of the host, a threshold density of viral surface proteins may also be critical for the recognition by germline B cells for efficient mounting of humoral responses. The encapsulated genetic material may also stimulate B cells through the Toll-like receptors. Substantial mechanistic studies at the single-molecule level and imaging of live cells have revealed the sensitivity of B cells to the density of antigens. However, at the mechanistic level, it remains largely uncharacterized how B cells may recognize and respond to the individual as well as collective attributes of a virus, including the spatial density of proteins and the internal nucleic acids. This project aims to unravel the cellular and molecular mechanisms of B cell responses to viral features both in vivo and in vitro, using a new generation of model particulate antigens that we have recently developed. The success of this project will yield new and important mechanistic information on how B cells recognize particulate antigens similar to viruses, and reveal the functional outcomes of B cells in response to the recognition of the biophysical features of these antigens.