Nucleic Acids Research, Vol 27, Issue 11 2304-2309, Copyright © 1999 by Oxford University Press
M Larijani, CC Yu, R Golub, QL Lam and GE Wu
It has long been appreciated that some immunoglobulin (and T-cell receptor)
gene segments are used much more frequently than others. The VHsegment V81x
is a particularly striking case of overusage. Its usage varies with the
stage of B-cell development and with the strain of mice, but it is always
high in B cell progenitors. We have found that the coding sequence and the
recombination signal sequences (RSS) are identical in five mouse strains,
including CAST/Ei, a strain derived from the species Mus castaneus. Thus,
the strain differences cannot be attributed to sequences within V81x
itself. V81x RSS mediated recombination at rates significantly higher than
another VHRSS. Although the V81x nonamer differs at one base pair from the
consensus sequence, an RSS with this nonamer and a consensus heptamer
recombines as well as the consensus RSS. When the V81x spacer is replaced
by that of VA1, the frequency of recombination decreases by approximately
5- fold; thus, the contribution of variation in natural spacers to
variability in VHusage in vivo is likely to be more than has been
previously appreciated. Furthermore, the contribution of the heptamer and
nonamer to differential VHusage in our assay is correlated inversely with
their conservation throughout the VHlocus.
ARTICLES
The role of components of recombination signal sequences in immunoglobulin gene segment usage: a V81x model
Department of Immunology and Ontario Cancer Institute, University of Toronto, Room 8-111, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. mani1@oci.utoronto.ca
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