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Blood, 15 February 2001, Vol. 97, No. 4, pp. 1001-1008
IMMUNOBIOLOGY
Ordered recombination of immunoglobulin light chain genes
occurs at the IGK locus but seems less strict at the
IGL locus
Mirjam van der Burg,
Talip Tümkaya,
Marjan Boerma,
Sandra de
Bruin-Versteeg,
Anton W. Langerak, and
Jacques J. M. van
Dongen
From the Department of Immunology, Erasmus University
Rotterdam/ University Hospital Rotterdam, Rotterdam, The Netherlands.
Regulation of allelic and isotypic exclusion of human
immunoglobulin (Ig) light-chain genes was studied in 113 chronic B-cell leukemias as a "single-cell" model that allowed complete analysis of each light chain allele. Our data show that monospecific Ig light
chain expression is in about 90% of cases determined by ordered
recombination: Ig gene (IGK) rearrangements, followed by
IGK deletions and Ig gene (IGL)
rearrangements, resulting in the presence of only one functional Ig
light chain rearrangement. In about 10% (10 cases), 2 functional Ig
light chain rearrangements (IGK/IGL or IGL/IGL,
but not IGK/IGK) were identified. This might be explained
by the fact that regulation of the ordered recombination process is not
fully strict, particularly when the IGL locus is involved.
Unfavorable somatic mutations followed by receptor editing might have
contributed to this finding. Eight of these 10 cases indeed contained
somatic mutations. In cases with 2 functional Ig light chain
rearrangements, both alleles were transcribed, but monospecific Ig
expression was still maintained. This suggests that in these cases
allelelic exclusion is not regulated at the messenger RNA level but
either at the level of translation or protein stability or via
preferential pairing of Ig light and Ig heavy chains. Nevertheless,
ordered rearrangement processes are the main determinant for
monospecific Ig light chain expression.
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