Direct in vivo VH to JH rearrangement violating the 12/23 rule.
V(D)J recombination at the immunoglobulin heavy chain (IgH) locus follows the 12/23 rule to ensure the correct assembly of the variable region gene segments. Here, we report characterization of an in vivo model that allowed us to study recombination violating the 12/23 rule, namely a mouse strain lacking canonical D elements in its IgH locus. We demonstrate that VH to JH joining can support the generation of all B cell subsets. However, the process is inefficient in that B cells and antibodies derived from the DH-less allele are not detectable if the latter is combined with a wild-type IgH allele. There is no preferential usage of any particular VH gene family or JH element in VHJH junctions, indicating that 23/23-guided recombination is possible, but is a low frequency event at the IgH locus in vivo.
Koralov
Sergei B
SB
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.
Novobrantseva
Tatiana I
TI
Hochedlinger
Konrad
K
Jaenisch
Rudolf
R
Rajewsky
Klaus
K
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic
D000906:Antibodies; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region