Antibodies play an essential role in defending vertebrates against infectious agents and toxins, but can also induce or exacerbate disease, especially when they have specificity for self molecules. To better control antibody production, so that it can always be used to the host's advantage, more needs to be learned about the natural mechanism by which B lymphocytes, which have the capacity to differentiate into antibody secreting cells, are activated. This proposal will use in vivo and in vitro polyclonal and antigen-specific systems to study the roles played by B cell sIg and other surface molecules, lymphokines and monokines, MHC restricted, antigen- specific T help, and naturally occurring polyclonal activator substances in inducing B cells to 1) change their expression of surface receptors, 2) increase in size, 3) synthesize DNA, 4) continue to proliferate and increase in number, 5) secrete immunoglobulin, and 6) switch from IgM to IgG secretion. Special attention will be paid to: 1) the better definition of differences in the roles played by B cell sIgM and sIgD, 2) the exploration of synergism and antagonism between different B cell activating stimuli, 3) the study of differences and similarities in the ways that B cells are activated in in vitro and in vivo experimental systems, and 4) the elucidation of whether direct cell to cell contact is required for maximal activation of B lymphocytes. Special features of these studies include 1) the use of size defined populations of B lymphocytes, 2) the use of B cells from mice with defined genetic defects that influence B cell activation, 3) the use of a well characterized in vivo model in which B cells can be polyclonally activated by affinity purified antibodies to IgM or IgD, 4) the use of B cell activating, monoclonal antibodies to the Lyb2 B cell surface antigen, and 5) the use of a panel of nine monoclonal anti-IgD antibodies that differ in their abilities to bind to and crosslink IgD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021328-02
Application #
3131315
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-09-30
Project End
1988-02-29
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. Uniformed Services University of Health Science
Department
Type
Schools of Medicine
DUNS #
City
Bethesda
State
MD
Country
United States
Zip Code
20814
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