The goal of this project is to characterize the function of B lymphocyte membrane molecules. Previous findings indicated that the FcGamma receptors of B lymphocytes interact with: a) the lymphocyte cytoskeleton, b) Ia antigens, c) Lym antigens, d) surface IgM, and e) surface IgD. Each of these interactions is distinct, specific, and non-random. Studies with a B lmyphocyte hybridoma (2.4G2) have shown that this hybridoma produces a low molecular weight substance(s) which triggers B lymphocytes to both proliferative and secrete antibody. This result suggests that certain B lymphocytes may produce factor(s) with helper activity. Studies utilizing antigen-antibody complexes and monoclonal anti-Fcy receptor antibodies indicate that B lymphocyt FcGamma receptors cross-liniked by their physiologic ligand down-regulate B lymphocyte differentiation without affecting proliferation. Resting but not activated B lymphocytes are susceptible to this negative regulation. Occupancy of B lymphocyte surface IgM by a separate ligand is necessary for inhibition to occur, suggesting that the previously described interaction between these two membrane receptors is involved in generating the negative signal. Monoclonal anti-Fcy receptor antibodies on a Sepharose matrix but not in soluble form effect B lymphocyte function in a fashion similar to antigen antibody complexes. This result suggests that certain monoclonal antibodies specific for cell surface receptors must be presented in a form which will produce effective cross-linking in order to obtain functional effects. Covalently cross-linked monoclonal antibodies are being prepared to test this hypothesis. Recently, several monoclonal antibodies have been produced which react primarily with activated B lymphocytes. The molecules recognized by these antibodies will be characterized chemically and functionally. These molecules may be receptors for growth or differentiation factors.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB005035-13
Application #
4691753
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code