title: Acute and chronic B cell depletion disrupts CD4+ and CD8+ T cell homeostasis and expansion during acute viral infection in mice.
abstract: B cells provide humoral protection against pathogens and promote cellular immunity through diverse nonclassical effector functions. To assess B cell function in promoting T cell homeostasis, mature B cells were either acutely or chronically depleted in mice using CD20 mAb. Acute B cell depletion in either 2- or 4-mo-old mice significantly reduced spleen and lymph node CD4(+) and CD8(+) T cell numbers, including naive, activated, and Foxp3(+)CD25(+)CD4(+) regulatory T cell subsets. The numbers of IFN-γ- and TNF-α-producing T cells were also significantly reduced. Chronic B cell depletion for 6 mo in aged naive mice resulted in a 40-70% reduction in activated CD4(+) and CD8(+) T cell numbers and 20-50% reductions in IFN-γ-producing T cells. Therefore, B cells were necessary for maintaining naive CD4(+) and CD8(+) T cell homeostasis for subsequent optimal T cell expansion in young and old mice. To determine the significance of this finding, a week of B cell depletion in 4-mo-old mice was followed by acute viral infection with lymphocytic choriomeningitis virus Armstrong. Despite their expansion, activated and cytokine-producing CD4(+) and CD8(+) T cell numbers were still significantly reduced 1 wk later. Moreover, viral peptide-specific CD4(+) and CD8(+) T cell numbers and effector cell development were significantly reduced in mice lacking B cells, whereas lymphocytic choriomeningitis virus titers were dramatically increased. Thus, T cell function is maintained in B cell-depleted mice, but B cells are required for optimal CD4(+) and CD8(+) T cell homeostasis, activation, and effector development in vivo, particularly during responses to acute viral infection.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Jacquelyn M
authors.initials: JM
authors.lastname: Lykken
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: David J
authors.initials: DJ
authors.lastname: DiLillo
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Eric T
authors.initials: ET
authors.lastname: Weimer
authors.affiliation: Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033;
authors.forename: Susanne
authors.initials: S
authors.lastname: Roser-Page
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Mark T
authors.initials: MT
authors.lastname: Heise
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157; and.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Grayson
authors.affiliation: Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033; Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710; thomas.tedder@duke.edu.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
mesh_terms: D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma