title: CpG inhibits pro-B cell expansion through a cathepsin B-dependent mechanism.
abstract: TLR9 is expressed in cells of the innate immune system, as well as in B lymphocytes and their progenitors. We investigated the effect of the TLR9 ligand CpG DNA on the proliferation of pro-B cells. CpG DNA inhibits the proliferation of pro-B, but not pre-B, cells by inducing caspase-independent cell death through a pathway that requires the expression of cathepsin B. This pathway is operative in Rag-deficient mice carrying an SP6 transgene, in which B lymphopoiesis is compromised, to reduce the size of the B lymphocyte precursor compartments in the bone marrow. Thus, TLR9 signals can regulate B lymphopoiesis in vivo.
authors.affiliation: Unité du Développement des Lymphocytes, Département d'Immunologie, Institut Pasteur, Paris, France.
authors.forename: Ana Inés
authors.initials: AI
authors.lastname: Lalanne
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moraga
authors.forename: Yi
authors.initials: Y
authors.lastname: Hao
authors.forename: João Pedro
authors.initials: JP
authors.lastname: Pereira
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Alves
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Freitas
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.forename: Paulo
authors.initials: P
authors.lastname: Vieira
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020169:Caspases / Q000502:physiology; D002401:Cathepsin B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D018899:CpG Islands / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D015851:Interleukin-7 / Q000502:physiology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D015851:Interleukin-7; D008024:Ligands; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D020169:Caspases; D002401:Cathepsin B; C533915:Ctsb protein, mouse