Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection
Memory B cells are comprised of unswitched (CD27+IgD+) and switched (CD27+IgD-) subsets. The origin and function of unswitched human memory B cells are debated in the literature, whereas switched memory B cells are primed to respond to recurrent infection. Unswitched memory B cells have been describ...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1213344/full |
| _version_ | 1797745327200010240 |
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| author | Moriah J. Castleman Adriana Luna Santos Kelsey E. Lesteberg Kelsey E. Lesteberg James P. Maloney William J. Janssen William J. Janssen Kara J. Mould Kara J. Mould J. David Beckham J. David Beckham J. David Beckham Roberta Pelanda Raul M. Torres |
| author_facet | Moriah J. Castleman Adriana Luna Santos Kelsey E. Lesteberg Kelsey E. Lesteberg James P. Maloney William J. Janssen William J. Janssen Kara J. Mould Kara J. Mould J. David Beckham J. David Beckham J. David Beckham Roberta Pelanda Raul M. Torres |
| author_sort | Moriah J. Castleman |
| collection | DOAJ |
| description | Memory B cells are comprised of unswitched (CD27+IgD+) and switched (CD27+IgD-) subsets. The origin and function of unswitched human memory B cells are debated in the literature, whereas switched memory B cells are primed to respond to recurrent infection. Unswitched memory B cells have been described to be reduced in frequency with severe SARS-CoV2 infection and here we characterize their activation status, BCR functionality, and contribution to virally-induced cytokine production. Analyses of whole blood from healthy individuals, people immunized against SARS-CoV2, and those who have had mild and severe SARS-CoV2 infection, confirm a reduction in the frequency of unswitched memory B cells during severe SARS-CoV2 infection and demonstrate this reduction is associated with increased levels of systemic TNFα. We further document how severe viral infection is associated with an increased frequency of ‘IgD+’ only memory B cells that correlate with increased IgG autoantibody levels. Unswitched and switched memory B cells from severe SARS-CoV2 infection displayed evidence of heightened activation with a concomitant reduction in the expression of the inhibitory receptor CD72. Functionally, both populations of memory B cells from severe SARS-COV2 infection harbored a signaling-competent BCR that displayed enhanced BCR signaling activity in the unswitched population. Finally, we demonstrate that B cells from mild SARS-CoV2 infection are poised to secrete pro-inflammatory cytokines IL-6 and TNFα. Importantly, unswitched memory B cells were a major producer of IL-6 and switched memory B cells were a major producer of TNFα in response to viral TLR ligands. Together these data indicate that B cells contribute to the inflammatory milieu during viral infection. |
| first_indexed | 2024-03-12T15:22:39Z |
| format | Article |
| id | doaj.art-3fcc280c7b4545769308a4722574f5b1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T15:22:39Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3fcc280c7b4545769308a4722574f5b12023-08-11T01:12:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12133441213344Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infectionMoriah J. Castleman0Adriana Luna Santos1Kelsey E. Lesteberg2Kelsey E. Lesteberg3James P. Maloney4William J. Janssen5William J. Janssen6Kara J. Mould7Kara J. Mould8J. David Beckham9J. David Beckham10J. David Beckham11Roberta Pelanda12Raul M. Torres13Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Medicine, Division of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine, University of Colorado, Aurora, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine, University of Colorado, Aurora, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Medicine, Division of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, United StatesRocky Mountain Regional VA, Medical Center, Aurora, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United StatesMemory B cells are comprised of unswitched (CD27+IgD+) and switched (CD27+IgD-) subsets. The origin and function of unswitched human memory B cells are debated in the literature, whereas switched memory B cells are primed to respond to recurrent infection. Unswitched memory B cells have been described to be reduced in frequency with severe SARS-CoV2 infection and here we characterize their activation status, BCR functionality, and contribution to virally-induced cytokine production. Analyses of whole blood from healthy individuals, people immunized against SARS-CoV2, and those who have had mild and severe SARS-CoV2 infection, confirm a reduction in the frequency of unswitched memory B cells during severe SARS-CoV2 infection and demonstrate this reduction is associated with increased levels of systemic TNFα. We further document how severe viral infection is associated with an increased frequency of ‘IgD+’ only memory B cells that correlate with increased IgG autoantibody levels. Unswitched and switched memory B cells from severe SARS-CoV2 infection displayed evidence of heightened activation with a concomitant reduction in the expression of the inhibitory receptor CD72. Functionally, both populations of memory B cells from severe SARS-COV2 infection harbored a signaling-competent BCR that displayed enhanced BCR signaling activity in the unswitched population. Finally, we demonstrate that B cells from mild SARS-CoV2 infection are poised to secrete pro-inflammatory cytokines IL-6 and TNFα. Importantly, unswitched memory B cells were a major producer of IL-6 and switched memory B cells were a major producer of TNFα in response to viral TLR ligands. Together these data indicate that B cells contribute to the inflammatory milieu during viral infection.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1213344/fullunswitched memoryswitched memoryB cellsCOVID - 19SARS-CoV- 2human |
| spellingShingle | Moriah J. Castleman Adriana Luna Santos Kelsey E. Lesteberg Kelsey E. Lesteberg James P. Maloney William J. Janssen William J. Janssen Kara J. Mould Kara J. Mould J. David Beckham J. David Beckham J. David Beckham Roberta Pelanda Raul M. Torres Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection Frontiers in Immunology unswitched memory switched memory B cells COVID - 19 SARS-CoV- 2 human |
| title | Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection |
| title_full | Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection |
| title_fullStr | Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection |
| title_full_unstemmed | Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection |
| title_short | Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection |
| title_sort | activation and pro inflammatory cytokine production by unswitched memory b cells during sars cov 2 infection |
| topic | unswitched memory switched memory B cells COVID - 19 SARS-CoV- 2 human |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1213344/full |
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