Memory cells are difficult to functionally define in human subjects. Humanized mice that have received implants of human thymus and fetal liver generate a human immune system and spontaneously respond to endogenous and environmental antigens to generate cells with the phenotype of presumed IgM memory/activated B cells and class-switched memory/activated B cells. We will use an immunization and BrdU labeling strategy to identify antigen-specific B cells that retain BrdU label over extended periods in order to functionally define human IgM memory and class-switched memory cells. Controversies regarding the origins of human IgM+CD27+ B cells may also be resolved in similar studies on humanized mice.

Public Health Relevance

Relevance Defining and understanding the origins of human memory B cells will help the development of novel and rational approaches for vaccine generation. These cells are also linked to a number of human B lineage malignancies and understanding the biology of these naturally long-lived B cells will be of importance from a lymphomagenesis standpoint.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI088478-01
Application #
7876327
Study Section
Special Emphasis Panel (ZRG1-IMM-J (02))
Program Officer
Ferguson, Stacy E
Project Start
2010-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$265,500
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Pillai, Shiv; Mattoo, Hamid; Cariappa, Annaiah (2011) B cells and autoimmunity. Curr Opin Immunol 23:721-31