La. Elenich et al., GAMMA-1 HEAVY-CHAIN TRANSGENES ARE RESPONSIVE TO IFN-GAMMA REPRESSIONAND CD40 LIGATION, The Journal of immunology, 158(10), 1997, pp. 4564-4573
The cis-acting elements that regulate production of germ-line transcri
pts from Ig heavy chain genes and subsequent switch recombination to t
hose genes are poorly defined, We reported that a 17-kb transgene that
includes I gamma 1, S gamma 1, and C gamma 1 is regulated for germ-li
ne transcription like the endogenous gamma 1 gene. Transcripts from su
ch transgenes are expressed only in B cells treated with both LPS and
IL-4, and not in B cells treated with LPS alone or in thymocytes or no
nlymphoid tissues, We have now found that transcripts from these trans
genes are induced by treatment of transgenic B cells by IL-4 alone, As
reported by others, IFN-gamma acts to inhibit the IL-4-mediated induc
tion of germ-line transcripts of the endogenous gamma 1 gene. We have
found that LPS-plus IL-4-induced germ-line transcription of gamma 1 tr
ansgenes is likewise inhibited by treatment of B cells with IFN-gamma,
so the gamma 1 gene must include the cis-acting element(s) that confe
rs this inhibition. It is also known that CD40 ligation induces a mode
st amount of germ-line transcripts from the endogenous gamma 1 gene an
d synergizes with IL-4 to induce large amounts of germ-line transcript
s, The gamma 1 transgenes are likewise induced by CD40 ligation, sugge
sting that the response element(s) for CD40 ligation can be found in t
he gamma 1 gene. The promoter region for the germ-line transcripts and
the I exon are likely to include some of these cis-acting elements. A
series of transgenic mice with the promoter/I gamma 1 region conferre
d low level, lymphoid-specific, RNA expression to a reporter gene, inc
luding significant expression in thymocytes. However, the promoter/I g
amma 1 transgenes were not regulated like the endogenous gamma 1 gene,
in that transcription in splenic B cells was not increased by LPS plu
s IL-4.