Bone marrow B cell apoptosis during in vivo influenza virus infection requires TNF-alpha and lymphotoxin-alpha.
Suppression of bone marrow myeloid and erythroid progenitor cells occurs after infection with a variety of different viruses. In this study, we characterize the alterations in bone marrow (BM) lymphocytes after influenza virus infection in mice. We found a severe loss of BM B cells, particularly CD43(low/-)B220(+) pre-B and immature B cells, in influenza virus-infected mice. Depletion of BM B lineage cells resulted primarily from cell cycle arrest and most likely apoptosis within the BM environment, rather than from increased trafficking of BM emigrants to peripheral lymphoid tissues. Use of gene-knockout mice indicates that depletion of BM B cells is dependent on TNF-alpha, lymphotoxin-alpha, and both TNF receptors, TNFR1-p55 and TNFR2-p75. Thus, TNF-alpha and lymphotoxin-alpha are required for loss of BM B lineage cells during respiratory infection with influenza virus.
Sedger
Lisa M
LM
Department of Molecular Immunology, Immunex, Seattle, WA 98101, USA.
Hou
Sam
S
Osvath
Sarah R
SR
Glaccum
Moira B
MB
Peschon
Jacques J
JJ
van Rooijen
Nico
N
Hyland
Lisa
L
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle; D002454:Cell Differentiation; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000472:pathogenicity / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D015703:Antigens, CD; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha