The Ig(kappa) enhancer influences the ratio of Ig(kappa) versus Ig(lambda) B lymphocytes.
We generated mice harboring germline mutations in which the enhancer element located 9 kb 3' of the immunoglobulin kappa light chain gene (3'E kappa) was replaced either by a single loxP site (3'E kappa delta) or by a neomycin resistance gene (3'E kappa N). Mice homozygous for the 3'E(kappa delta) mutation had substantially reduced numbers of kappa-expressing B cells and increased numbers of lambda-expressing B cells accompanied by decreased kappa versus lambda gene rearrangement. In these mutant mice, kappa expression was reduced in resting B cells, but was normal in activated B cells. The homozygous 3'E(kappa)N mutation resulted in a similar but more pronounced phenotype. Both mutations acted in cis. These studies show that the 3'E(kappa) is critical for establishing the normal kappa/lambda ratio, but is not absolutely essential for kappa gene rearrangement or, surprisingly, for normal kappa expression in activated B cells. These studies also imply the existence of additional regulatory elements that have overlapping function with the 3'E(kappa) element.
Gorman
J R
JR
Howard Hughes Medical Institute, The Children's Hospital, Boston, Massachusetts 02115, USA.
van der Stoep
N
N
Monroe
R
R
Cogne
M
M
Davidson
L
L
Alt
F W
FW
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains