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Unité du Développement des Lymphocytes (Centre National de la Recherche Scientifique, URA 1961), Institut Pasteur, Paris, France
Ig H chain (IgH) allelic exclusion remains a puzzling topic. Here,
we address the following question: Do phenotypic IgH allelically
included cells exist in normal mice and, if so, at what frequency?
Sorted cells from heterozygous mice were evaluated for the expression
of both IgM allotypes by double intracytoplasmic stainings. Dual
expressors were found at a frequency of 1 in 104 splenic B
cells. These data were confirmed by direct sequencing of IgH-rearranged
alleles obtained after single cell (or clone) PCR on dual expressors.
Typically, these cells have one rearranged J558 VH whereas,
in the other allele, a D-proximal VH gene is used.
Interestingly, dual expressors have rearranged IgH alleles with similar
CDR3 lengths. These results show that, in contrast to the 
L chain
and the TCR 
-chain, IgH allelic exclusion is the result of an
extremely stringent mechanism. We discuss two non-mutually exclusive
scenarios for the origin of IgH dual expressors: 1) IgH allelically
included cells arise when the first allele to rearrange productively is
unable to form a pre-BCR; dual expressors could be a subset of this
population in which, upon conventional L chain rearrangement, both IgH
are expressed at the surface; and 2) synchronous rearrangement of the
IgH alleles.
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