Transforming growth factor-beta induced class switch recombination may be modified during the cell proliferation restored by IL-2 stimulation.
Mouse spleen cells were stimulated, first by transforming growth factor beta (TGF-beta) and then by interleukin-2 (IL-2) in the presence of bacterial lipopolysaccharide (LPS). LPS plus IL-2 stimulation restored the cell proliferation suppressed by TGF-beta and increased the number of B cells. Both TGF-beta alone or TGF-beta plus IL-2 enhanced production of surface IgA-positive (sIgA+) cells in LPS-stimulated B-cell cultures. We characterized extrachromosomal circular DNAs generated in TGF-beta-primed and IL-2-stimulated B cells and identified the breakpoints of S mu/S gamma 3 recombinants which were the major intermediates of S mu and S alpha switch recombination. All switch recombination sites were dispersed evenly within both S mu and S gamma 3 regions. This even distribution of S mu/S gamma 3 breakpoints is in contrast to the site preference of class switch breakpoints induced by TGF-beta alone. These results suggest that IL-2-stimulated cell proliferation may modify class switch recombination primed by TGF-beta.
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
T
T
Iwasato
Y
Y
Kanari
A
A
Shimizu
T
T
Honjo
H
H
Yamagishi
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D004270:DNA, Circular; D005260:Female; D005803:Genes, Immunoglobulin; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D013154:Spleen / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*
D017931:DNA Primers; D004270:DNA, Circular; D007070:Immunoglobulin A; D007376:Interleukin-2; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta