The Bone Marrow Functions as the Central Site of Proliferation for Long-Lived NK Cells

Mary J. G. van Helden, Natascha de Graaf, Claire J. P. Boog, David J. Topham, Dietmar M. W. Zaiss, Alice J. A. M. Sijts*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

NK cells play an important role in the early defense against invading pathogens. Although it is well established that infection leads to a substantial, local increase in NK cell numbers, little is known about the mechanisms that trigger their proliferation and migration. In this study, we investigated the dynamics of NK cell responses after intranasal respiratory virus infection. We show that NK cell numbers increased in the airways after influenza virus infection but find no evidence of proliferation either at the site of infection or in the draining lymph nodes. Instead, we find that the bone marrow (BM) is the primary site of proliferation of both immature and mature NK cells during infection. Using an adoptive transfer model, we demonstrate that peripheral, long-lived and phenotypically mature NK cells migrate back to the BM and proliferate there, both homeostatically and in response to infection. Thus, the BM is not only a site of NK cell development but also an important site for proliferation of long-lived mature NK cells.

Original languageEnglish
Pages (from-to)2333-2337
Number of pages5
JournalJournal of Immunology
Volume189
Issue number5
DOIs
Publication statusPublished - 1 Sep 2012

Keywords

  • NATURAL-KILLER-CELLS
  • CD8(+) T-CELLS
  • RESPIRATORY SYNCYTIAL VIRUS
  • HOMEOSTATIC PROLIFERATION
  • ACTIVATING RECEPTORS
  • BACTERIAL-INFECTION
  • INFLUENZA INFECTION
  • IFN-GAMMA
  • MEMORY
  • TRAFFICKING

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