Cell Reports (Oct 2013)

Bisphosphonates Target B Cells to Enhance Humoral Immune Responses

  • Elena Tonti,
  • Nereida Jiménez de Oya,
  • Gabriele Galliverti,
  • E. Ashley Moseman,
  • Pietro Di Lucia,
  • Angelo Amabile,
  • Stefano Sammicheli,
  • Marco De Giovanni,
  • Laura Sironi,
  • Nicolas Chevrier,
  • Giovanni Sitia,
  • Luigi Gennari,
  • Luca G. Guidotti,
  • Ulrich H. von Andrian,
  • Matteo Iannacone

DOI
https://doi.org/10.1016/j.celrep.2013.09.004
Journal volume & issue
Vol. 5, no. 2
pp. 323 – 330

Abstract

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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.