Idiotypes are serological markers of antibody V regions and thus in principle allow the analysis of the expression and selection of antibody V regions in the immune system. The questions we are asking in this proposal are: (a) Is the idiotype repertoire at the B cell level a direct correlation with the genetic information in the antibody structural genes? (b) Are B cells selected according to their receptor idiotype when they leave the bone marrow and enter the peripheral immune system? (c) How are B cells selected in antigen-driven immune responses and, specifically, are idiotypic interactions involved in this selection? (d) If idiotypic interactions are involved in B cell selection at any stage, what is its mechanism? In order to try to answer the first question we will perform oligonucleotide-directed mutagenesis of Clambdal gene of BALB/c origin, which is found expressed in about 5 percent of the toal immunoglobulins. A single base change will transform it to a Clambdal gene like the one of SJL/J mice which phenotypically is low or negative for the expression of lambdal light chains. Experiments addressing the other questions will be performed using two experimental mice models. A substrain of SJL/J found by M. Potter and R. Lieberman called SJL/P will be used. In spite of the fact that these two substrains are quite similar concerning many phenotypic markers, they differ at the Clambdal gene. SJL/P have the Clambdal gene like in BALB/c and can make Clambdal light chains. The question we address is whether SJL/P can now make anti-NP antibodies that are NPb positive, since they no longer have the lambdal light chain defect. Another animal model that we will use will be C57BL/6 mice that have in its germ line a functionally rearranged VHNP gene which codes for NPa positive heavy chains. Cellular experiments are suggested in order to address the question as to whether network interactions are operating via the Ig-receptors on B cells.
