We recently identified a novel population of flu-specific, lung-resident memory B cells (BRM cells) that are phenotypically different than systemic memory B cells, reside in unique sites in the lung and respond more rapidly to challenge infection than their systemic counterparts. Interestingly, lung BRM cells provide a significant degree of protection to challenge infection, even when they do not cross-react with the HA and NA proteins of the challenge virus, suggesting that BRM cells have additional effector functions beyond antibody (Ab) production. In fact, B cells make inflammatory cytokines like IFN?, lymphotoxin, OX40L and IL-6, as well as anti-inflammatory cytokines like IL-10, IL-27 and IL-35. Moreover they are potent APCs, particularly for their cognate antigens. Thus, BRM cells have a variety of mechanisms, in addition to Ab, to modulate inflammation and promote anti- viral immunity. The experiments in this proposal will investigate the mechanisms used by flu-specific BRM cells to clear virus and protect the lung and will determine how pulmonary vaccination can elicit and maintain BRM cells in the lung.

Public Health Relevance

. The experiments in this proposal will examine the functions of memory B cells that live in the lung and respond to influenza infection and compare them with memory B cells that live at systemic sites. We will also determine how various vaccination strategies enhance or impair the formation of memory B cells in the lung, experiments that are critically important for understanding how and when vaccines should be administered in the respiratory tract.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI153413-01
Application #
10033774
Study Section
Immunity and Host Defense (IHD)
Program Officer
Lane, Mary Chelsea
Project Start
2020-06-16
Project End
2025-05-31
Budget Start
2020-06-16
Budget End
2021-05-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Genetics
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294