The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published 7 February 2005. doi:10.1084/jem.20041577
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 3, 341-348
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BRIEF DEFINITIVE REPORT

 Direct in vivo VH to JH rearrangement violating the 12/23 rule

Sergei B. Koralov1, Tatiana I. Novobrantseva1, Konrad Hochedlinger2, Rudolf Jaenisch2, and Klaus Rajewsky1

1 The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115
2 Whitehead Institute for Biomedical Research, Cambridge, MA 02142

CORRESPONDENCE Klaus Rajewsky: rajewsky{at}cbr.med.harvard.edu

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.

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.


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