Restraint of B cell activation by Foxj1-mediated antagonism of NF-kappa B and IL-6.
The forkhead transcription factor Foxj1 inhibits spontaneous autoimmunity, in part by antagonizing NF-kappaB activation in T cells. We demonstrate here that Foxj1 also inhibits humoral immune responses intrinsically in B cells; Foxj1 deficiency in B cells results in spontaneous and accentuated germinal center formation, associated with the development of pathogenic autoantibodies and accentuated responses to immunizations-all reflecting excessive activity of NF-kappaB and its target gene IL-6, and correlating with a requirement for Foxj1 to regulate the inhibitory NF-kappaB component IkappaBbeta. Thus, Foxj1 restrains B cell activation and the maturation of humoral responses, demonstrating a critical role for at least this forkhead transcription factor in the regulation of B lymphocyte homeostasis.
Lin
Ling
L
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Brody
Steven L
SL
Peng
Stanford L
SL
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors; D015850:Interleukin-6 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D016328:NF-kappa B; D014157:Transcription Factors; D000093242:Interleukin-6 Inhibitors; C481963:FOXJ1 protein, mouse