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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