High frequency of normal DJH joints in B cell progenitors in severe combined immunodeficiency mice

doi:10.1084/jem.178.3.1007

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High frequency of normal DJH joints in B cell progenitors in severe combined immunodeficiency mice

JL Pennycook, Y Chang, J Celler, RA Phillips and GE Wu
Department of Immunology, University of Toronto, Ontario, Canada.

The severe combined immunodeficiency (scid) mouse has a defective V(D)J recombinase activity that results in arrested lymphoid development at the pro-B cell stage in the B lineage. The defect is not absolute and scid mice do attempt gene rearrangement. Indeed, approximately 15% of all scid mice develop detectable levels of oligoclonal serum immunoglobulin and T cell activity. To gain more insight into the scid defect and its effect on V(D)J rearrangement, we analyzed DJH recombination in scid bone marrow. We determined that DJH structures are present in scid bone marrow and occur at a frequency only 10-100 times less than C.B-17+/+. The scid DJH repertoire is limited and resembles fetal liver DJH junctions, with few N insertions and predominant usage of reading frame 1. Moreover, 70% of the DJH structures were potentially productive, indicating that normal V(D)J recombinants should be arising continually.
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