NK cells and B lymphocytes interact with each other in a mutually productive manner. Whereas B lymphocytes can induce purified NK cells to produce IFNgamma, NK cells can secrete a differentiative factor for B cells. In order to identify the interactive molecules involved we wish to first clone the B cell determinant which induces NK cells using a new mutant cell line that has lost the inductive capacity. This ligand can then be used to investigate the nature of the receptor on NK cells. Secondly, we wish to further investigate the in vivo significance of the effect of activated NK cells on antigen specific responses by analyzing the in vivo parameters involved in their interaction with B cells and to directly test whether the skewing of the isotype distribution to IgG2a affects the efficiency of antibody dependent cytotoxicity (ADCG) against specific tumor targets in vivo. Finally, we wish to investigate the role of NK cells in the maintenance of non specific immunoglobulin levels in animals that are compromised in T cell help. Since this help may be related to the growth regulation of NK cells in vivo we will also study the regulation of expression of the lL-2 receptor genes because changes in expression of the lL-2 receptor components are the most likely candidates involved in controlling NK cell growth. These studies should provide further insight into the two diverse yet related roles of Nk cells, that of immune regulation and defense against foreign insult.