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Septic Shock Shapes B Cell Response toward an Exhausted-like/Immunoregulatory Profile in Patients

Claude-Alexandre Gustave, Morgane Gossez, Julie Demaret, Thomas Rimmelé, Alain Lepape, Christophe Malcus, Françoise Poitevin-Later, Laurent Jallades, Julien Textoris, Guillaume Monneret and Fabienne Venet
J Immunol April 1, 2018, 200 (7) 2418-2425; DOI: https://doi.org/10.4049/jimmunol.1700929
Claude-Alexandre Gustave
Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 69437 Lyon, France;EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Joint Research Unit, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;
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Morgane Gossez
Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 69437 Lyon, France;EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Joint Research Unit, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;
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Julie Demaret
Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 69437 Lyon, France;EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Joint Research Unit, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;
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Thomas Rimmelé
EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Joint Research Unit, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Hospices Civils de Lyon, Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, 69437 Lyon, France;
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Alain Lepape
Hospices Civils de Lyon, Intensive Care Unit, Lyon-Sud Hospital, 69310 Pierre-Bénite, France; and
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Christophe Malcus
Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 69437 Lyon, France;
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Françoise Poitevin-Later
Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 69437 Lyon, France;
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Laurent Jallades
Hospices Civils de Lyon, Hematology Laboratory, Lyon-Sud Hospital, 69310 Pierre-Bénite, France
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Julien Textoris
EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Joint Research Unit, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Hospices Civils de Lyon, Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, 69437 Lyon, France;
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Guillaume Monneret
Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 69437 Lyon, France;EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Joint Research Unit, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;
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Fabienne Venet
Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 69437 Lyon, France;EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;Joint Research Unit, Claude Bernard Lyon 1 University, bioMérieux, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437 Lyon, France;
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Abstract

Septic shock is accompanied by the development of immune dysfunctions whose intensity and duration are associated with increased risk of secondary infections and mortality. Although B lymphocytes play a pivotal role in the immune response to infections, no comprehensive exploration of circulating B cell status has been performed during the immunosuppressive phase of septic shock. Thus, our aim was to extensively characterize the phenotype and function of B cells in septic shock, including IL-10 production. Circulating B lymphocyte phenotype and function were evaluated by flow cytometry on fresh whole blood and after ex vivo stimulation in adult septic shock patients sampled at day 1, 3, and 6 after the onset of shock. The circulating B cell number was reduced in septic shock patients, whereas the B cell proportion among total lymphocytes was increased. The remaining circulating B lymphocytes presented with decreased MHC class II expression and increased CD21low CD95high exhausted-like phenotype but showed no change in maturation status. Circulating B cell functions were markedly altered after sepsis with reduced ex vivo activation and proliferation capacities. Finally, B cell response after septic shock was characterized by a clear plasmacytosis and an increased IL-10 production in remaining B cells from patients after ex vivo stimulation. During the sepsis-induced immunosuppression phase, B cell response is altered and is oriented toward an exhausted-like/immunoregulatory profile. Further studies are now needed to confirm the immunoregulatory properties of B lymphocytes and evaluate their role in sepsis-induced immunosuppression.

Footnotes

  • This work was sponsored by funds from the Hospices Civils de Lyon (to G.M., F.V., A.L., and T.R.).

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    AB/C
    Ab bound per cell
    EdU
    5-ethynyl-2′-deoxyuridine
    EFS
    Etablissement Français du Sang
    HV
    healthy volunteer
    ICU
    intensive care unit
    IQR
    interquartile range
    MFI
    median fluorescence intensity
    mHLA-DR
    monocyte HLA-DR
    PB
    Pacific Blue
    SSC
    side scatter.

  • Received June 28, 2017.
  • Accepted January 26, 2018.
  • Copyright © 2018 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 200 (7)
The Journal of Immunology
Vol. 200, Issue 7
1 Apr 2018
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Septic Shock Shapes B Cell Response toward an Exhausted-like/Immunoregulatory Profile in Patients
Claude-Alexandre Gustave, Morgane Gossez, Julie Demaret, Thomas Rimmelé, Alain Lepape, Christophe Malcus, Françoise Poitevin-Later, Laurent Jallades, Julien Textoris, Guillaume Monneret, Fabienne Venet
The Journal of Immunology April 1, 2018, 200 (7) 2418-2425; DOI: 10.4049/jimmunol.1700929

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Septic Shock Shapes B Cell Response toward an Exhausted-like/Immunoregulatory Profile in Patients
Claude-Alexandre Gustave, Morgane Gossez, Julie Demaret, Thomas Rimmelé, Alain Lepape, Christophe Malcus, Françoise Poitevin-Later, Laurent Jallades, Julien Textoris, Guillaume Monneret, Fabienne Venet
The Journal of Immunology April 1, 2018, 200 (7) 2418-2425; DOI: 10.4049/jimmunol.1700929
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Print ISSN 0022-1767        Online ISSN 1550-6606