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B-chronic lymphocytic leukemias can undergo isotype switching in vivo and
can be induced to differentiate and switch in vitro [see comments]
F Malisan, AC Fluckiger, S Ho, C Guret, J Banchereau and H Martinez-Valdez
Laboratory for Immunological Research, Schering Plough, Dardilly, France.
B-chronic lymphocytic leukemias (B-CLL) represent expanded clones of
resting B lymphocytes that mostly express surface IgM (sIgM). The present
study shows that B-CLL cells, freshly isolated from two patients, were
sIgM+, sIgG-, and sIgA- but expressed IgG and IgA transcripts. cDNA cloning
and sequencing showed that the VDJ segments associated to gamma and alpha
heavy chain transcripts are identical to those from mu transcripts, thus
showing that B lymphocytes giving rise to CLL cells have undergone isotype
switching in vivo. Stimulation of these B-CLL cells through surface CD40 in
the presence of interleukin- 10 induced them to secrete IgG and IgA,
proving that they can also differentiate into Ig-secreting cells. Finally,
CD40-stimulated B-CLL cells were induced to switch towards IgE in response
to interleukin-4, as shown by the presence of specific VDJ-C epsilon
transcripts and the secretion of IgE. Therefore, B-CLL cells tested herein
can undergo isotype switching in vivo and can be induced to undergo further
isotype switching and differentiation in vitro.
Volume 87,
Issue 2,
pp. 717-724,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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