Somatic diversity of the immunoglobulin repertoire is controlled in an isotype-specific manner

We have studied two aspects of the IgE immune response. First, we have comp ared the kinetics of the IgE response to the T cell-dependent antigen ph-Ox coupled to ovalbumin with that of the IgG1 response and we have assessed t he quality of the IgE response. Second, we have studied the generation of s omatic diversity, understood as the combined effect of somatic mutation and the selection of D(iversity) and J(oining) elements, in germinal center B cells at the molecular level, using the germ-line sequence of the prototype anti-ph-Ox heavy chain variable element V(H)Ox1 as reference. We evaluated sequences derived from mu-, gamma1- and epsilon -variable elements and sho wed that somatic diversification was different for all isotypes studied. We further compared the IgE responses of wild-type mice with those of mice ex pressing a truncated cytoplasmic IgE tail (IgE(KVK Delta tail)). IgE(KVK De lta tail) mice showed a more diverse sequence pattern. We corroborated prev ious results suggesting that short CDR3 regions are indicative for high-aff inity antibodies by measuring relative affinities of phage-expressed Fab fr agments with prototype long and short CDR3 regions. Therefore, the composit ion of the antigen-receptor is responsible for the selection process and th e expansion of antigen-specific cells, leading to an isotype-specific antib ody repertoire.