H. Tokuyama et Y. Tokuyama, RETINOIC ACID INDUCES THE EXPRESSION OF GERM-LINE C-ALPHA TRANSCRIPT MAINLY BY A TGF-BETA-INDEPENDENT MECHANISM, Cellular immunology, 176(1), 1997, pp. 14-21
The effects of retinoic acid (RA) on expression of germ-line transcrip
ts, I alpha C alpha and I gamma 1C gamma 1, and of IgA and IgG1 mRNAs
by murine surface IgM-positive B-cells were examined by reverse transc
riptase-polymerase chain reaction (RT-PCR). LPS-stimulated B-cells wer
e cultured for 2-3 days in the presence of IL-4 and IL-5 with or witho
ut RCL Total RNA was extracted from the cells, and RT-PCR specific for
the germ-line transcripts was carried out. RA strongly induced mature
germ-line C alpha transcript (I alpha C alpha) at concentrations betw
een 10 and 100 nM. On the other hand, RA completely inhibited IL-4-ind
uced I gamma 1C gamma 1 expression. Significant induction of I alpha C
alpha was observed even at a low RA concentration (0.2 nM) in the pre
sence of LPS (1.5-5 mu g/ml) and without cytokines, and three- to four
fold stimulation of I alpha C alpha induction was seen at 5 nM. I alph
a C alpha expression induced by RA (10 nM) and LPS (1.5 mu g/ml) was n
ot significantly affected by addition of anti-TGF-beta 1 and anti-TGF-
beta 2 neutralizing antibodies, although that induced by TGF-beta 1 or
TGF-beta 2 was completely inhibited by these antibodies. These result
s suggest that the major induction pathway of I alpha C alpha was not
mediated by active TGF-beta and that RA at physiological concentration
s may be involved in IgA isotype switching in vivo in a TGF-beta-indep
endent manner. (C) 1997 Academic Press.