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*
Department of Microbiology, University of Texas Health Science Center, San Antonio, TX 78284; and
Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Department of Medicine, Harvard Medical School, Boston, MA 02115
Transcription of the germline C
1 and C
Ig genes is believed
to be a necessary prerequisite for isotype switching to IgG1 and IgE,
respectively. IL-4 stimulation and ligation of CD40 can each
independently induce low level germline 1 and transcription in
murine B cells. Together these signals act synergistically to promote
high level germline transcription and are normally required for
T-dependent isotype switching to IgG1 and IgE. The STAT6 transcription
factor has been suggested to play a critical role in IL-4-induced
activation of germline C1 and C genes. To directly assess the
role of STAT6 in IL-4R- and CD40-mediated germline transcription and
switching, we have analyzed these events in splenic B cells from
STAT6-deficient mice. Our results demonstrate that IL-4 does not induce
detectable levels of germline 1 or transcripts in
STAT6-deficient B cells. Germline transcript expression induced by CD40
stimulation alone is unaffected, but synergism between CD40- and
IL-4R-mediated signals is completely ablated. Switch recombination to
S1, as measured by digestion-circularization PCR, is dramatically
reduced in STAT6-deficient B cells stimulated with CD40 ligand plus
IL-4. Similarly, germline 1 transcript expression and switch
recombination to S1 are also impaired in STAT6-deficient B cells
stimulated with IL-4, IL-5, and anti-IgD Abs conjugated to dextran,
a model for T-independent type II responses. These results directly
demonstrate a critical role for STAT6 in the IL-4-mediated activation
of germline Ig gene transcription and switch recombination in
nontransformed B cells.
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|
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