Reevaluation of 3'Ekappa function in stage- and lineage-specific rearrangement and somatic hypermutation.
Transgenic studies have led to the conclusion that the 3'Ekappa enhancer functions to suppress kappa variable region gene assembly in T lineage cells and in progenitor B cells and have also implicated 3'Ekappa as a critical element in promoting somatic hypermutation of kappa variable region genes. To assess the role of the endogenous 3'Ekappa, we assayed these processes in mice homozygous for mutations in which the 3'Ekappa sequences were deleted by the loxP/Cre method (3'Ekappa delta/delta mice). In contrast to transgenic findings, we found that deletion of the endogenous 3'Ekappa did not deregulate kappa gene rearrangement in T lineage cells or in pro-B cells. Furthermore, immunization of the 3'Ekappa delta/delta mice led to the generation of specific antibodies with mutation patterns typical of affinity maturation, showing that there is no absolute requirement for the 3'Ekappa with respect to somatic mutation of endogenous kappa genes.
van der Stoep
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N
Department of Genetics, Harvard Medical School, The Children's Hospital, Boston, Massachusetts 02115, USA.
Gorman
J R
JR
Alt
F W
FW
D000818:Animals; D001483:Base Sequence; D019070:Cell Lineage / Q000235:genetics* / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains