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.
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7 February 2005
Brief Definitive Report|
February 07 2005
Direct in vivo VH to JH rearrangement violating the 12/23 rule
Sergei B. Koralov,
Sergei B. Koralov
1The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
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Tatiana I. Novobrantseva,
Tatiana I. Novobrantseva
1The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
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Konrad Hochedlinger,
Konrad Hochedlinger
2Whitehead Institute for Biomedical Research, Cambridge, MA 02142
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Rudolf Jaenisch,
Rudolf Jaenisch
2Whitehead Institute for Biomedical Research, Cambridge, MA 02142
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Klaus Rajewsky
Klaus Rajewsky
1The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
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Sergei B. Koralov
1The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
Tatiana I. Novobrantseva
1The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
Konrad Hochedlinger
2Whitehead Institute for Biomedical Research, Cambridge, MA 02142
Rudolf Jaenisch
2Whitehead Institute for Biomedical Research, Cambridge, MA 02142
Klaus Rajewsky
1The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
CORRESPONDENCE Klaus Rajewsky: [email protected]
S.B. Koralov and T.I. Novobrantseva contributed equally to this work.
T.I. Novobrantseva's present address is Biogen Idec, Inc., Cambridge, MA 02142.
Received:
August 06 2004
Accepted:
November 29 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 201 (3): 341–348.
Article history
Received:
August 06 2004
Accepted:
November 29 2004
Citation
Sergei B. Koralov, Tatiana I. Novobrantseva, Konrad Hochedlinger, Rudolf Jaenisch, Klaus Rajewsky; Direct in vivo VH to JH rearrangement violating the 12/23 rule . J Exp Med 7 February 2005; 201 (3): 341–348. doi: https://doi.org/10.1084/jem.20041577
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