Abstract
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 orb 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).
Original language | English (US) |
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Pages (from-to) | 1295-1305 |
Number of pages | 11 |
Journal | Journal of Experimental Medicine |
Volume | 189 |
Issue number | 8 |
DOIs | |
State | Published - Apr 19 1999 |
Keywords
- Allelic exclusion
- B cell differentiation
- Immunoglobulin transgenic mice
- V(D)J rearrangement
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology