The factors underlying the formation of long-lived antibody secreting cells (ASCs) or plasma cells are unknown. The main objective of this R21 application is to establish whether ASCs that form during the earliest phases of the humoral immune response to T cell dependent (TD) and T cell independent (TI) antigens are long-lived. The proposed experiments will follow from preliminary data suggesting that both TD and TI antigens elicit the formation of long-lived ASCs. Additional experiments will test whether ASCs that form in response to T cell independent antigen require migration into the bone marrow to become long-lived. We will address these questions using a combination of normal and genetically manipulated mouse lines. Specifically we will: 1) Define the lifespan of early ASCs produced via primary TI and TD antigens, and 2) Define the lifespan of TI-1 antigen-induced ASCs retained in the spleen.

Public Health Relevance

The factors underlying the generation of long-lived antibody secreting plasma cells are not understood. Our studies will challenge current dogma that T cell independent antigens fail to induce the formation of long-lived plasma cells. These studies have direct implications for therapeutic strategies to combat antibody-mediated autoimmune diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI090700-02
Application #
8066726
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Ferguson, Stacy E
Project Start
2010-06-01
Project End
2013-05-31
Budget Start
2011-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2011
Total Cost
$190,954
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Bortnick, Alexandra; Chernova, Irene; Quinn 3rd, William J et al. (2012) Long-lived bone marrow plasma cells are induced early in response to T cell-independent or T cell-dependent antigens. J Immunol 188:5389-96