Natural antibodies sustain differentiation and maturation of human dendritic cells.
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.
Bayry
Jagadeesh
J
Institut National de la Santé et de la Recherche Médicale Unité 430 and Université Pierre et Marie Curie, Institut des Cordeliers, 75006 Paris, France.
Lacroix-Desmazes
Sébastien
S
Donkova-Petrini
Vladimira
V
Carbonneil
Cédric
C
Misra
Namita
N
Lepelletier
Yves
Y
Delignat
Sandrine
S
Varambally
Sooryanarayana
S
Oksenhendler
Eric
E
Lévy
Yves
Y
Debré
Marianne
M
Kazatchkine
Michel D
MD
Hermine
Olivier
O
Kaveri
Srini V
SV
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
D000906:Antibodies; D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand