Volume 271, Number 29,
Issue of July 19, 1996
pp. 17404-17410
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Inducing the Loss of Immunoglobulin
Light Chain Production
and the Rearrangement of a Previously Excluded Allele in Human Plasma B
Cell Lines with Concanavalin A
(Received for publication, December 29, 1995, and in revised form, April 3, 1996)
Hirofumi
Tachibana
,
Yoshitaka
Ushio
,
Chatchadaporn
Krungkasem
and
Sanetaka
Shirahata
From the Graduate School of Genetic Resources Technology, Kyushu
University, 6-10-1, Hakozaki, Fukuoka, Japan
We investigated the expression of differential
light chains in human B cell lines secreting immunoglobulin (Ig).
When these cell lines were cultured with concanavalin A for a long
period of time, a subpopulation of some but not all of these cell lines
was induced to express new
light chains replacing the original
chain (light chain shifting). Production of the new
chain, which
replaces the original
chain, results from a VJ rearrangement at a
previously excluded allele and a dramatic reduction of the original
chain transcript, although no difference was found in the level of
heavy chain transcript. Recombination activating genes RAG-1
and RAG-2, which are normally expressed during
specific early stages of lymphocyte development, were expressed in not
only the light chain shifting-inducible lines but also in the
non-inducible cells. Treatment of these Ig secreting cell lines with
dibutyryl cAMP, which is known to enhance expression of the RAG
genes, could not induce the creation of new
light
chain-producing cells from the inducible lines, suggesting that the
expression of the two RAG genes is not sufficient for
inducing new
light chain production. Concanavalin A induced a
gradual but significant production lost of the original
chain in a
subpopulation of the light chain shifting-inducible cells but not in
the non-inducible cells. Association of new
light chain production
with loss of original
chain raises the possibility that, when the
RAG genes are expressed, concanavalin A may act on a novel
intracellular mechanism controlling
light chain allelic exclusion
in these plasma cell lines.