Bisphosphonates target B cells to enhance humoral immune responses

Cell Rep. 2013 Oct 31;5(2):323-30. doi: 10.1016/j.celrep.2013.09.004. Epub 2013 Oct 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibody Formation / drug effects
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Diphosphonates / pharmacology*
  • Humans
  • Immunity, Humoral / drug effects*
  • Immunoglobulin G / metabolism
  • Inflammasomes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Signal Transduction
  • Toll-Like Receptors / metabolism
  • Vesiculovirus / immunology


  • Adjuvants, Immunologic
  • Diphosphonates
  • Immunoglobulin G
  • Inflammasomes
  • Toll-Like Receptors

Associated data

  • GEO/GSE50403