Acute and chronic B cell depletion disrupts CD4+ and CD8+ T cell homeostasis and expansion during acute viral infection in mice

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2014-07, Vol.193 (2), p.746-756
Main Authors: Lykken, Jacquelyn M, DiLillo, David J, Weimer, Eric T, Roser-Page, Susanne, Heise, Mark T, Grayson, Jason M, Weitzmann, M Neale, Tedder, Thomas F
Format: Article
Language:English
Subjects:
Acute Disease
Animals
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cell Proliferation
Flow Cytometry
Forkhead Transcription Factors - immunology
Forkhead Transcription Factors - metabolism
Homeostasis - immunology
Host-Pathogen Interactions - immunology
Interferon-gamma - immunology
Interferon-gamma - metabolism
Interleukin-2 Receptor alpha Subunit - immunology
Interleukin-2 Receptor alpha Subunit - metabolism
Lymph Nodes - immunology
Lymph Nodes - metabolism
Lymphocyte Count
Lymphocyte Depletion
Lymphocytic Choriomeningitis - immunology
Lymphocytic Choriomeningitis - virology
Lymphocytic choriomeningitis virus
Lymphocytic choriomeningitis virus - immunology
Lymphocytic choriomeningitis virus - physiology
Mice
Mice, Inbred C57BL
Spleen - immunology
Spleen - metabolism
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - metabolism
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1302848