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Unité de Génétique et Biochimie du Développement, Unité de Recherche Associée Centre National de la Recherche Scientifique 1960, Département d’Immunologie, Institut Pasteur, Paris, France; and
Anatomy Department, University of Birmingham Medical School, Edgbaston, Birmingham, United Kingdom
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 
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 V and J 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 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.
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