Requirement for Runx proteins in IgA class switching acting downstream of TGF-beta 1 and retinoic acid signaling.
IgA is a specific isotype required for mucosal immunity and is the most abundant Ab produced in vivo. Recently, several inductive signals for IgA class switch recombination have been identified; however, the molecular details of the action of these signals and the specific factors acting in B cells remain elusive. In this study, we show that combination of retinoic acid (RA) and TGF-beta1 with other factors induced a much higher frequency of IgA-switched cells than reported previously. In addition, IgA production is severely impaired in Runx2-Runx3 double-deficient mice. In Runx2-Runx3-deficient B cells, both RA- and TGF-beta1-dependent inductions of alpha germline transcription are completely blocked. These data suggest that Runx proteins play an essential role in IgA class switching acting downstream of RA and TGF-beta1 signaling.
Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto University, Sakyo-ku, Kyoto, Japan.
Kakeru
K
Watanabe
Manabu
M
Sugai
Yukiko
Y
Nambu
Motomi
M
Osato
Tatsunari
T
Hayashi
Miho
M
Kawaguchi
Toshihisa
T
Komori
Yoshiaki
Y
Ito
Akira
A
Shimizu
D000818:Animals; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011995:Recombination, Genetic / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D014212:Tretinoin / Q000502:physiology*
D050659:Core Binding Factor Alpha 1 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D007070:Immunoglobulin A; C493716:Runx2 protein, mouse; C493730:Runx3 protein, mouse; D053773:Transforming Growth Factor beta1; D014212:Tretinoin