description): After commitment to the B cell lineage, B cell development is controlled by a set of well described checkpoints. B cell antigen receptors (BCR) regulate many different physiologically significant processes in the antibody system. The BCR is composed of the immunoglobulin (Ig) which is responsible for ligand binding and a signaling complex, Ig alpha and Ig beta. Previous studies have shown that Ig alpha and Ig beta are present in the earliest B cell progenitors. Other studies have also shown that the Ig alpha-Ig beta complex associates with mu to form an active complex, a surrogate BCR. This allows signaling at the pre-B cell stage. Transgenic and gene targeting experiments have shown the importance of these signaling molecules in both early and late B cell development. These studies, however, were limited in their ability to reconstitute the B cell system, and to study the specific roles of Ig alpha and Ig beta in B cell development. The overall goal of this project is to elucidate the molecular mechanisms that control Ig alpha and Ig beta in the context of a normally assembled BCR in vivo. The working hypothesis is that mIgu crosslinking leads to the phosphorylation of the ITAMS of Ig alpha and Ig beta to activate allelic exclusion and the pre-B cell transition but their role later in B cell development is still unclear. To address these questions we created a mutation by gene targeting that truncates the cytoplasmic domain of Ig beta (Igbetacytodelta). The overall aim of these studies is threefold. 1) Determine the effect of the Igbetacytodelta mutation on B cell development. 2) Examine the immune responses of these Igbetacytodelta mice. 3) Examine the downstream signaling events after Ig crosslinking. These studies will give us a greater understanding of the roles of Ig alpha and Ig beta in B cell development and B cell effector function.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD039848-01
Application #
6233080
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Lock, Allan
Project Start
2001-04-11
Project End
2003-03-31
Budget Start
2001-04-11
Budget End
2002-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$83,500
Indirect Cost
Name
Rockefeller University
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065