The overall goal of the proposed research is to explore the regulation of T-independent antibody responses by T-cells. To this end, we will use the recently developed, in vitro T-independent response of A/J mice to azobenzenearsonate conjugated Brucella abortus (ABA-Bru). Preliminary studies revealed 3 characteristics of this system: approximately 50% of the anti-ABA plaque forming cells (PFC) are inhibited by a rabbit anti-idiotype antiserum, the system is suppressed by both antigen-specific and idiotype-specific T-cells, idiotype-specific helper T-cells increase the numbers of idiotype positive (CRI mu plus) PFC, and the idiotypic quality of the response is controlled by endogenous regulatory T-cell circuits. In the first phase of the proposed investigation,the cellular regulatory elements will be defined using standard T-cell markers including antisera of the Ly sub t series. Simultaneously, the B-cell subset responding to ABA-Bru will be determined by serotyping and by functional criteria. The second phase of the research will focus on establishing continuous regulatory T-cell lines using both hybridoma and T-cell growth factor methodology. The third period of investigation will center on the molecular nature of T-cell regulation by using molecules derived from the continuous T-cell lines to modulate the anti-ABA Bru response. During this phase, special emphasis will be placed on the relationships between T-cell antigen receptors and their cognate regulatory molecules. In the final phase of investigation, the relationships between induced regulatory T-cells and endogenous T-cell circuits will be probed by searching for induced-type regulatory molecules in normal cell populations responding to ABA-Bru.