Chromatin Remodeling at the Ig Loci Prior to V(D)J Recombination

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Abstract
Rearrangement of Ig H and L chain genes is highly regulated and takes place sequentially during B cell development. Several lines of evidence indicate that chromatin may modulate accessibility of the Ig loci for V(D)J recombination. In this study, we show that remodeling of V and J segment chromatin occurs before V(D)J recombination at the endogenous H and κ L chain loci. In recombination-activating gene-deficient pro-B cells, there is a reorganization of nucleosomal structure over the H chain JH cluster and increased DNase I sensitivity of VH and JH segments. The pro-B/pre-B cell transition is marked by a decrease in the DNase I sensitivity of VH segments and a reciprocal increase in the nuclease sensitivity of Vκ and Jκ segments. In contrast, JH segments remain DNase I sensitive, and their nucleosomal organization is maintained in μ+ recombination-activating gene-deficient pre-B cells. These results indicate that initiation of rearrangement is associated with changes in the chromatin structure of both V and J segments, whereas stopping recombination involves changes in only V segment chromatin. We further find an increase in histone H4 acetylation at both the H and κ L chain loci at the pro-B cell stage. Although histone H4 acetylation appears to be an early change associated with B cell commitment, acetylation alone is not sufficient to promote subsequent modifications in Ig chromatin.