It is not known how the immune system develops during ontogeny to become a connected network of interacting T and B cells. The long-term goal of this on-going research project is to solve this problem using the T15/PC murine system as a model. Our working hypothesis is that there exist finite resources allocated to B cell differentiation during ontogeny. As a consequence, B cell precursors compete with each and some become winners (dominant idiotypes). T15+ B cell clones have an ontogenetic advantage and compete successfully to reach a developmental stage where IghC-linked network selection occurs to preserve dominant expression of this idiotype. This proposal deals with experiments designed to reconstruct the cellular interactions that bring about T15 dominance. I propose a series of in vivo experiments to analyze the role of antigen, internal images of PC, helper T and B cell subsets in the regulation of T15 expression. Our research addresses important and unresolved issues in immunoregulation: idiotype vs non-idiotype-specific effects, the development of the lymphocyte network and the interdependence of T and B cell repertoires.
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