The purpose of the proposed study is to delineate the immunobiological mechanisms whereby anti-idiotypic antibodies regulate normal and malignant B lymphocytes activity. Three particular problems will be investigated: (1) the properties of anti-idiotypic antibodies that determine their capacity to modulate normal idiotype expression; (2) the contribution of host immune function to the anti-idiotype-induced suppression of idiotype production; and (3) the ability of anti-idiotype reagents to control the growth and differentiation of continuous B lymphoma-like cell lines. To facilitate these studies, our collection of monoclonal anti-idiotypic antibodies will be expanded to include reagents which differ significantly from one another only with respect to isotype, specificity or affinity. A panel of idiotype-positive lymphoma-like lines representing different stages of B cell differentiation (as characterized by cell surface phenotype) will also be produced. The monoclonal antibody reagents will be compared In Vivo using the idiotype system in which A/J mice are challenged with the hapten azophenylarsonate. Comparisons will include the capacity to regulate primary vs. secondary responses, interactions with host NK and ADCC cells. The same monoclonal reagents will be tested In Vivo and In Vitro with regard to their capacity to regulate the growth of the homogeneous B lymphoma lines. In this case, it will be possible to examine membrane events such as patching or capping which occur immediately subsequent to antibody exposure. Overall, these investigations should contribute to the basic understanding of B cell activation and deactivation and should have clinical application with regard to the control of a variety of autoimmune and malignant diseases.
