B cells are responsible for maintaining humoral immunity. However, a comprehensive spatial map of murine and human B cell subsets across tissue compartments in the body is lacking. A barrier to these studies has been the lack of methods for comprehensive analysis of large numbers of cells from many different tissues and also access to rare human specimens. Here we use advanced computing and unbiased approaches to organize B cell subset and their signaling properties in mouse and man. We will test the hypothesis that B cell subset composition can be predicted by tissue site and that long-lived PCs in different tissues sites have distinct regulatory programs that reflect their unique microenvironments.
In Aim 1, we will establish the population structure of murine and human B lineage subsets throughout the body using unbiased approaches.
In Aim 2, we will establish the tissue-specific regulatory programs and clonal relationships of murine long-lived PC (LLPC) derived from two distinct microenvironments, BM versus gut. Results from this study will reveal the global population structure of B subsets responsible for humoral immunity and provide insights into how B cells control infections regionally and systemically.

Public Health Relevance

Improving human health requires knowledge of which immune subsets are in different tissues and how these cells receive signals from the environment. Studies here will map B cell subsets across different tissue in mouse and man, and examine how tissue site of origin influences signaling pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI145064-02
Application #
10000015
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Ferguson, Stacy E
Project Start
2019-08-21
Project End
2023-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15260