The objective is to study the development of the idiotype network during the ontogeny of mice. The focus in our work is on the role of T helper cells which recognize the dominant T15 idiotype in the response of BALB/c mice to phosphorylcholine (PC). The hypothesis to be tested states that early in ontogency, germ line encoded B cell idiotypes influences the repertoire of regulatory T cells. The proposed role of regulatory, idiotype recognizing T cells is to maintain a basic B cell repertoire necessary to preserve a functional network. We have established assays to measure T help of idiotype recognizing T cells for B cells responding to an idiotype hapten carrier antigen. We have observed that T15 specific helper cells recognize a shared idiotope which is expressed by the heavy chain. We also defined an inducer T cell which primes the idiotype recognizing helper cell. The specificity of the inducer T cells is anti-idiotypic. This T-T cell circuit can be triggered by PC antigen and may therefore be involved in the response to bacterial PC containing antigens. We propose to prepare T cell line, clones and hybridomas, which are idiotype specific. We will test these cell lines for their fine specificity, MHC restriction and role as regulatory idiotypes in the response to PC in vivo and in vitro. Monoclonal anti-idiotypes of defined biological activities will be administered to neonatal mice and the alteration of the network in the response to PC in the B and T cell compartments will be analyzed. One of the anti-idiotopes expresses the internal image of PC, i.e., is an Ab2Beta. The precursor frequency of T15 recognizing T helper cells will be followed as a neonatally manipulated mature mice; further, the idiotype fine specificity will be analyzed. A search for T suppressor cells will also be done using adoptive transfer protocols developed earlier in our lab. Finally, transgenic mice will be prepared to study the effect of idiotype and anti-idiotype expressing genes on the ontogeny of the immune network. This approach allows us to manipulate the immune system at a time in ontogeny before any rearrangements and committments to idiotype expression is made in B and T cells. We expect tha these idiotype manipulations will have profound effects on the development of the network. We will analyze these alterations by focusing on the T15/PC response in both the T helper cell and the B cell compartments.
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