The intraclonal diversity and control of antibody isotype switch recombination

The configuration of the expressed and unexpressed IgH alleles within two groups of hybridomas, both derived from single clones of B cells at an intermediate stage of the immune response of one mouse, were characterized. The data obtained confirm that individual 'naive' B cells are totipotent in their capacity to generate, via deletions in the IgH locus, offspring that express different IgG isotypes. Further, the number of distinct isotype switch deletions that took place during the proliferation and differentiation of these clones was enormous. Nevertheless, switching within one clone occurred exclusively to the IgG1 isotype at expressed and unexpressed IgH alleles. The data support the conclusion that, despite the fact that isotype switch recombination is occurring on a global scale within responding clones during the immune response, exclusive intraclonal expression of only one isotype can result from the direct control of the switching process.