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J. Exp. Med.,
Volume 189, Number 8, April 19, 1999 1295-1305
By
From the * Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; and the Here we show that suppression of VH-DJH rearrangement in mice bearing a µ heavy (H)
chain transgene (µ-tg mice) is associated with an extended period of DH-JH rearrangement,
the first step of Immunoglobulin H chain gene rearrangement. Whereas DH-JH rearrangement is
normally initiated and completed at the pro-B cell stage, in µ-tg mice it continues beyond this
stage and occurs most frequently at the small (late) pre-B stage. Despite ongoing DH-JH rearrangement in late pre-B cells of µ-tg mice, VH-DJH rearrangement is not detectable in these
cells. We infer that the lack of VH-DJH rearrangement primarily reflects tg-induced acceleration
of B cell differentiation past the stage at which rearrangement of VH elements is permissible. In
support of this inference, we find that the normal representation of early B lineage subsets is
markedly altered in µ-tg mice. We suggest that the effect of a productive VH-DJH rearrangement at an endogenous H chain allele may be similar to that of a µ-tg; i.e., cells that make a
productive VH-DJH rearrangement on the first attempt rapidly progress to a developmental
stage that precludes VH-DJH rearrangement at the other allele (allelic exclusion).
Department of
Microbiology, Arizona State University, Tempe, Arizona 85287
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