B lineage-restricted rearrangement of a human Ig kappa transgene.
To study the control of immunoglobulin kappa light chain gene rearrangement, we generated transgenic mice carrying a germ-line human kappa minilocus (HK) containing the J kappa-proximal V gene, V kappa IV, the V-J intergenic region, the five J kappa segments and the C kappa gene. This construct includes the intronic, but not the 3' kappa enhancer. Rearrangement of the HK transgene was found to be lymphoid specific and restricted to the B cell lineage. Quantification of kappa gene rearrangement in pre-B cell lines established from HK transgenic mice showed that, like endogenous kappa genes, rearrangement of the transgene is repressed in mu-negative early B cell precursors. These results indicate that rearrangement of the HK transgene is subjected to the same B/T cell and developmental regulation as V kappa-J kappa rearrangement at the endogenous locus. Comparison with an unrearranged kappa transgenic construct lacking the V-J intergenic region, suggests that this region, or elements associated with the proximal V gene, may act to restrict kappa gene rearrangement to the B cell lineage.
Cavelier
P
P
Unité de Génétique et Biochimie du Développement, URA CNRS 1960, Institut Pasteur, Paris, France.
Nato
F
F
Coquilleau
I
I
Rolink
A
A
Rougeon
F
F
Goodhardt
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D015870:Gene Expression / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D007133:Immunoglobulin Joining Region / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011995:Recombination, Genetic / Q000276:immunology; D019076:Transgenes / Q000276:immunology*
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains