title: Natural antibodies sustain differentiation and maturation of human dendritic cells.
abstract: The differentiation and maturation of dendritic cells (DCs) is governed by various signals in the microenvironment. Monocytes and DCs circulate in peripheral blood, which contains high levels of natural antibodies (NAbs). NAbs are germ-line-encoded and occur in the absence of deliberate immunization or microbial aggression. To assess the importance of NAbs in the milieu on DC development, we examined the status of DCs in patients with X-linked agammaglobulinemia, a disease characterized by paucity of B cells and circulating antibodies. We demonstrate that the in vitro differentiation of DCs is severely impaired in these patients, at least in part because of low levels of circulating NAbs. We identified NAbs reactive with the CD40 molecule as an important component that participates in the development of DCs. CD40-reactive NAbs restored normal phenotypes of DCs in patients. The maturation process induced by CD40-reactive NAbs was accompanied by an increased IL-10 and decreased IL-12 production. The transcription factor analysis revealed distinct signaling pathways operated by CD40-reactive NAbs compared to those by CD40 ligand. These results suggest that B cells promote bystander DC development through NAbs and the interaction between NAbs and DCs may play a role in steady-state migration of DCs.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 430 and Université Pierre et Marie Curie, Institut des Cordeliers, 75006 Paris, France.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Vladimira
authors.initials: V
authors.lastname: Donkova-Petrini
authors.forename: Cédric
authors.initials: C
authors.lastname: Carbonneil
authors.forename: Namita
authors.initials: N
authors.lastname: Misra
authors.forename: Yves
authors.initials: Y
authors.lastname: Lepelletier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delignat
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Marianne
authors.initials: M
authors.lastname: Debré
authors.forename: Michel D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood; D000906:Antibodies / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D005434:Flow Cytometry; D040181:Genetic Diseases, X-Linked / Q000097:blood; D006801:Humans; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand