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 collective attributes of a virus, including the spatial density of proteins and the internal nucleic acids. This project aims to test both functional and mechanistic relevance of viral features on B cell responses by developing quantitative assays both in vivo and in vitro. The success of this project will yield important mechanistic insights on how B cells may recognize particulate antigens similar in size to viruses and vaccines, and what are the possible functional outcomes of B cells in response to the recognition of these antigens.

Public Health Relevance

To understand the molecular and cellular mechanisms how protective immune responses are elicited by vaccines or invading pathogens would be useful for the design of vaccines. This project aims to study responses of B cells to particulate antigens, or mock viral particles, at molecular and cellular level. The successful completion of this project will fill in a gap in our knowledge regarding how B cells may be activated by viral pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI135559-01A1
Application #
9600127
Study Section
Cellular and Molecular Immunology - A Study Section (CMIA)
Program Officer
Ferguson, Stacy E
Project Start
2018-06-11
Project End
2020-05-31
Budget Start
2018-06-11
Budget End
2019-05-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Hua, Boyang; Wang, Yanbo; Park, Seongjin et al. (2018) The Single-Molecule Centroid Localization Algorithm Improves the Accuracy of Fluorescence Binding Assays. Biochemistry 57:1572-1576