Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID‐19 patients with pneumonia

Studies on the interactions between SARS‐CoV‐2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients...

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Bibliographic Details
Published in:European journal of immunology 2020-09, Vol.50 (9), p.1283-1294
Main Authors: De Biasi, Sara, Lo Tartaro, Domenico, Meschiari, Marianna, Gibellini, Lara, Bellinazzi, Caterina, Borella, Rebecca, Fidanza, Lucia, Mattioli, Marco, Paolini, Annamaria, Gozzi, Licia, Jaacoub, Dina, Faltoni, Matteo, Volpi, Sara, Milić, Jovana, Sita, Marco, Sarti, Mario, Pucillo, Carlo, Girardis, Massimo, Guaraldi, Giovanni, Mussini, Cristina, Cossarizza, Andrea
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antibodies, Viral - blood
Antibodies, Viral - classification
Antigens
B cells
B-Lymphocytes - immunology
B-Lymphocytes - virology
Betacoronavirus - immunology
Betacoronavirus - pathogenicity
C-Reactive Protein - immunology
carboxyfluorescein succinimidyl ester CFSE
Case-Control Studies
Cell activation
Cell number
Cell Proliferation
Coronavirus
Coronavirus Infections - immunology
Coronavirus Infections - mortality
Coronavirus Infections - pathology
Coronavirus Infections - virology
COVID-19
Cross-Sectional Studies
Cytokines - genetics
Cytokines - immunology
Female
Fibrin Fibrinogen Degradation Products - immunology
Flow cytometry
Humans
Humoral immunity
Immunity, Humoral
Immunoglobulin Isotypes - blood
Immunoglobulin M
Immunologic Memory
Immunological memory
Lung - immunology
Lung - pathology
Lung - virology
Lymphocyte Activation
Lymphocyte Count
Lymphocytes B
Male
Memory cells
Middle Aged
Organ Dysfunction Scores
Pandemics
Peripheral blood
Plasma levels
plasmablasts
Pneumonia
Pneumonia, Viral - immunology
Pneumonia, Viral - mortality
Pneumonia, Viral - pathology
Pneumonia, Viral - virology
Primary Cell Culture
principal component analysis (PCA)
principal components (PCs)
Principal components analysis
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Severity of Illness Index
Survival Analysis
Uniform Manifold Approximation and Projection (UMAP)
Vaccines
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Summary:Studies on the interactions between SARS‐CoV‐2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID‐19 pneumonia. COVID‐19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM+ and IgM− plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B‐cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C‐reactive protein, D‐dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B‐cell compartment could be one of the causes of the immunological failure to control SARS‐Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies. Through Principal Component Analysis combining clinical data with those regarding B cells, we identify important factors that tip the balance toward patient discharge or death. The window of opportunity represents the moment in which therapies that blocks IL‐6 pathway and acts on different cell types can be used.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.202048838