title: CD301b+dendritic cells suppress T follicular helper cells and antibody responses to protein antigens.
abstract: Strong antibody response is considered a hallmark of a successful vaccine. While dendritic cells (DCs) are important for T follicular helper (Tfh) cell priming, how this process is regulated in vivo is unclear. We show here that the depletion of CD301b+DCs specifically enhanced the development of Tfh cells, germinal center B cells and antibody responses against protein antigens. Exaggerated antibody responses in mice depleted of CD301b+DCs occurred in the absence of any adjuvants, and resulting antibodies had broader specificity and higher affinity to the immunogen. CD301b+DCs express high levels of PD-1 ligands, PD-L1 and PD-L2. Blocking PD-1 or PD-L1 during priming in wild-type mice partially mimicked the phenotype of CD301b+DC-depleted animals, suggesting their role in Tfh suppression. Transient depletion of CD301b+DC results in the generation of autoreactive IgG responses. These results revealed a novel regulatory mechanism and a key role of CD301b+DCs in blocking autoantibody generation.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, United States.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kumamoto
authors.affiliation: Department of Dermatology, University of Pittsburgh, Pittsburgh, United States.|Department of Immunology, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hirai
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, United States.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Wong
authors.affiliation: Department of Dermatology, University of Pittsburgh, Pittsburgh, United States.|Department of Immunology, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, United States.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Akiko
authors.identifier: http://orcid.org/0000-0002-7824-9856
authors.initials: A
authors.lastname: Iwasaki
keywords: Tfh; antibody; autoimmunity; dendritic cells; germinal center; immunology; immunoregulation; mouse