Bibliographic Details
| Title: |
Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection |
| Authors: |
Moriah J. Castleman, Adriana Luna Santos, Kelsey E. Lesteberg, James P. Maloney, William J. Janssen, Kara J. Mould, J. David Beckham, Roberta Pelanda, Raul M. Torres |
| Source: |
Frontiers in Immunology, Vol 14 (2023) |
| Publisher Information: |
Frontiers Media S.A., 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
unswitched memory, switched memory, B cells, COVID - 19, SARS-CoV- 2, human, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1213344/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2023.1213344 |
| Access URL: |
https://doaj.org/article/3fcc280c7b4545769308a4722574f5b1 |
| Accession Number: |
edsdoj.3fcc280c7b4545769308a4722574f5b1 |
| Database: |
Directory of Open Access Journals |
