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Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19
Open accessAbstract
Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ T FH cell differentiation together with an increase in T-bet+ T H1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ T FH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.
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“SARS-CoV-2 infection elicits a Th1 CD4+ T cell response, with IFNγ and IL-2 being the primary cytokines produced by these cells and some TNFα production as well112,126-129.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [129]
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“Consistent with a dominant extrafollicular B cell response, studies have consistently reported defective germinal center (GC) responses in the secondary lymphoid organs of patients who have succumbed to SARS-CoV-2 infection129,159.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [129]
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Metadata
- Authors
- Kaneko, N., Kuo, H.-H., Boucau, J., Farmer, J. R., Allard-Chamard, H., Mahajan, V. S., Piechocka-Trocha, A., Lefteri, K., Osborn, M., Bals, J., Bartsch, Y. C., Bonheur, N., Caradonna, T. M., Chevalier, J., Chowdhury, F., Diefenbach, T. J., Einkauf, K., Fallon, J., Feldman, J., Finn, K. K., Garcia-Broncano, P., Hartana, C. A., Hauser, B. M., Jiang, C., Kaplonek, P., Karpell, M., Koscher, E. C., Lian, X., Liu, H., Liu, J., Ly, N. L., Michell, A. R., Rassadkina, Y., Seiger, K., Sessa, L., Shin, S., Singh, N., Sun, W., Sun, X., Ticheli, H. J., Waring, M. T., Zhu, A. L., Alter, G., Li, J. Z., Lingwood, D., Schmidt, A. G., Lichterfeld, M., Walker, B. D., Yu, X. G., Padera, R. F., & Pillai, S.
- Affiliations
- Ragon Institute of MGH, MIT and Harvard (US)
- Brigham and Women's Hospital (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Corresponding author
- Padera, Robert F.
- Pillai, Shiv
- ORCID
- Kaneko, Naoki
- Kuo, Hsiao-Hsuan
- Boucau, Julie
- Farmer, Jocelyn R.
- Allard-Chamard, Hugues
- Mahajan, Vinay S.
- Osborn, Matthew
- Bals, Julia
- Bartsch, Yannic C.
- Caradonna, Timothy M.
- Chevalier, Josh
- Chowdhury, Fatema
- Diefenbach, Thomas J.
- Einkauf, Kevin
- Fallon, Jon
- Feldman, Jared
- Garcia-Broncano, Pilar
- Hartana, Ciputra Adijaya
- Hauser, Blake M.
- Jiang, Chenyang
- Lian, Xiaodong
- Liu, Hang
- Michell, Ashlin R.
- Rassadkina, Yelizaveta
- Seiger, Kyra
- Sessa, Libera
- Shin, Sally
- Singh, Nishant
- Sun, Weiwei
- Sun, Xiaoming
- Waring, Michael T.
- Zhu, Alex L.
- Alter, Galit
- Li, Jonathan Z.
- Lingwood, Daniel
- Schmidt, Aaron G.
- Lichterfeld, Mathias
- Walker, Bruce D.
- Yu, Xu G.
- Padera, Robert F.
- Pillai, Shiv
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 183
- Issue
- 1
- Pages
- 143-157.e13
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7437499
- OpenAlex
- W3049048202
- Cited by
- 734
- References
- 51
- Citations by year
- 2026: 31 · 2025: 48 · 2024: 69 · 2023: 105 · 2022: 174 · 2021: 244 · 2020: 62
- FWCI
- 19.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- COVID-19 pandemic, SARS-CoV-2, BCL6, T follicular helper cells, germinal center, humoral immune response, T-bet, Th1 cells, TNF-α, transitional B cells, follicular B cells, spleen, herd immunity
- MeSH terms
- COVID-19, Aged, Aged, 80 and over, B-Lymphocytes, Female, T-Lymphocytes, Helper-Inducer, Humans, Male, Middle Aged, Pneumonia, Viral, Spleen, Tumor Necrosis Factor-alpha, Coronavirus Infections, Germinal Center, Proto-Oncogene Proteins c-bcl-6, Pandemics
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