title: The bone marrow functions as the central site of proliferation for long-lived NK cells.
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.
authors: Division of Immunology, Faculty of Veterinary Medicine, University of Utrecht, 3584 CL Utrecht, The Netherlands.
authors: Mary J G
authors: MJ
authors: van Helden
authors: Natascha
authors: N
authors: de Graaf
authors: Claire J P
authors: CJ
authors: Boog
authors: David J
authors: DJ
authors: Topham
authors: Dietmar M W
authors: DM
authors: Zaiss
authors: Alice J A M
authors: AJ
authors: Sijts
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation