REEVALUATION OF 3'E-KAPPA FUNCTION IN STAGE-SPECIFIC AND LINEAGE-SPECIFIC REARRANGEMENT AND SOMATIC HYPERMUTATION

Transgenic studies have led to the conclusion that the 3'E-kappa enhan cer functions to suppress kappa variable region gene assembly in T lin eage cells and in progenitor B cells and have also implicated 3'E-kapp a as a critical element in promoting somatic hypermutation of kappa va riable region genes. To assess the role of the endogenous 3'E-kappa, w e assayed these processes in mice homozygous for mutations in which th e 3'E-kappa sequences were deleted by the loxP/Cre method (3'E(kappa)D elta/Delta mice). In contrast to transgenic findings, we found that de letion of the endogenous 3'E-kappa did not deregulate kappa gene rearr angement in T lineage cells or in pro-B cells. Furthermore, immunizati on of the 3'E(kappa)Delta/Delta mice led to the generation of specific antibodies with mutation patterns typical of affinity maturation, sho wing that there is no absolute requirement for the 3'E-kappa with resp ect to somatic mutation of endogenous kappa genes.