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Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses

Lundgren, Anna ; Leach, Susannah ; Axelsson, Hannes ; Isakson, Pauline ; Nyström, Kristina ; Scharf, Lydia ; Andersson, Bengt A ; Miron, Nicolae ; Marklund, Emelie and Andersson, Lars-Magnus , et al. (2023) In Clinical and Experimental Immunology 213(2). p.173-189
Abstract

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S)... (More)

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.

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publishing date
type
Contribution to journal
publication status
published
keywords
Humans, SARS-CoV-2, COVID-19, Immunoglobulin G, Immunoglobulin M, Antibodies, Viral, Antibodies, Neutralizing
in
Clinical and Experimental Immunology
volume
213
issue
2
pages
173 - 189
publisher
British Society for Immunology
external identifiers
  • scopus:85165521264
  • pmid:37071584
ISSN
0009-9104
DOI
10.1093/cei/uxad044
language
English
LU publication?
no
additional info
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.
id
32126fd7-139b-420d-bf4c-87ad88e3cbfd
date added to LUP
2023-11-16 12:43:38
date last changed
2024-04-14 17:00:01
@article{32126fd7-139b-420d-bf4c-87ad88e3cbfd,
  abstract     = {{<p>Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.</p>}},
  author       = {{Lundgren, Anna and Leach, Susannah and Axelsson, Hannes and Isakson, Pauline and Nyström, Kristina and Scharf, Lydia and Andersson, Bengt A and Miron, Nicolae and Marklund, Emelie and Andersson, Lars-Magnus and Gisslén, Magnus and Angeletti, Davide and Bemark, Mats}},
  issn         = {{0009-9104}},
  keywords     = {{Humans; SARS-CoV-2; COVID-19; Immunoglobulin G; Immunoglobulin M; Antibodies, Viral; Antibodies, Neutralizing}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{2}},
  pages        = {{173--189}},
  publisher    = {{British Society for Immunology}},
  series       = {{Clinical and Experimental Immunology}},
  title        = {{Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses}},
  url          = {{http://dx.doi.org/10.1093/cei/uxad044}},
  doi          = {{10.1093/cei/uxad044}},
  volume       = {{213}},
  year         = {{2023}},
}