title: Bisphosphonates target B cells to enhance humoral immune responses.
abstract: Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens, and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4(+) and γδ T cells, neutrophils, or dendritic cells, and their effect does not rely on local macrophage depletion, Toll-like receptor signaling, or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as an additional class of adjuvants that boost humoral immune responses.
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Tonti
authors.forename: Nereida
authors.initials: N
authors.lastname: Jiménez de Oya
authors.forename: Gabriele
authors.initials: G
authors.lastname: Galliverti
authors.forename: E Ashley
authors.initials: EA
authors.lastname: Moseman
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Lucia
authors.forename: Angelo
authors.initials: A
authors.lastname: Amabile
authors.forename: Stefano
authors.initials: S
authors.lastname: Sammicheli
authors.forename: Marco
authors.initials: M
authors.lastname: De Giovanni
authors.forename: Laura
authors.initials: L
authors.lastname: Sironi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chevrier
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sitia
authors.forename: Luigi
authors.initials: L
authors.lastname: Gennari
authors.forename: Luca G
authors.initials: LG
authors.lastname: Guidotti
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Matteo
authors.initials: M
authors.lastname: Iannacone
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects*; D007074:Immunoglobulin G / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D018116:Vesiculovirus / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D004164:Diphosphonates; D007074:Immunoglobulin G; D058847:Inflammasomes; D051193:Toll-Like Receptors