The immune response to the natural hapten, phosphocholine (PC), is derived from three different VL which pair with a single VH. Extensive diversity is found in the expressed antibodies of each VH/VL pair and is due to usage of different DH, junctional diversity and somatic point mutations. We have recently found that different PC-containing microbes stimulate preferential expression of one or two of the three VH/VL gene pairs. The most dramatic occurs in the PC-specific response to Proteus morganii in which only a single idiotype is expressed. Analysis of anti-PC mRNA isolated from hybridomas reveals that the mature response is confined to a single VH/VL gene pair and diversity is dependent on somatic mutation. The most striking finding is that the response in individual mice seems to originate from as few as one precursor B lymphocyte. Our main goal is to use this example of an immune response to evaluate the somatic evolution of antibody diversity. Using hybridoma methodology and molecular biological technics, we propose to investigate the clonality of the anti-PC response to P. morganii in order to gain an understanding of the origins of clonal diversity; the time of commitment of B cell precursors and the influence of environment on acquisition of commitment; the impact of antigen and somatic mutation on selection and clonal expansion; and the nature of regulatory cells that might contribute to clonal expansion and clonal dominance. We expect that new and significant information will also be forthcoming about the nature of B cell memory.
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