RECEPTOR EDITING IN A TRANSGENIC MOUSE MODEL - SITE, EFFICIENCY, AND ROLE IN B-CELL TOLERANCE AND ANTIBODY DIVERSIFICATION

Mice carrying transgenic rearranged V region genes in their IgH and Ig kappa loci to encode an autoreactive specificity direct the emerging autoreactive progenitors into a pre-B cell compartment, in which their receptors are edited by secondary V kappa-J kappa rearrangements and RS recombination. Editing is an efficient process, because the mutant mice generate normal numbers of B cells. In a similar nonautoreactive transgenic strain, neither a pre-B cell compartment nor receptor editi ng was seen. Thus, the pre-B cell compartment may have evolved to edit the receptors of autoreactive cells and later been generally exploite d for efficient antibody diversification through the invention of the pre-B cell receptor, mimicking an autoreactive antibody to direct the bulk of the progenitors into that compartment.