The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
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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Self-citationInto the Eye of the Cytokine Storm
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Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals
Robbiani, D. F., Gaebler, C., Muecksch, F., Lorenzi, J. C. C., Wang, Z., Cho, A., Agudelo, M., Barnes, C. O., Gazumyan, A., Finkin, S., et al. (2020) · Nature · doi:10.1038/s41586-020-2456-9 · Cited by 1,853
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A serological assay to detect SARS-CoV-2 seroconversion in humans
Amanat, F., Stadlbauer, D., Strohmeier, S., Nguyen, T. H. O., Chromikova, V., McMahon, M., Jiang, K., Arunkumar, G. A., Jurczyszak, D., Polanco, J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0913-5 · Cited by 1,769
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“In persons with COVID-19, the magnitude and durability of antibody responses are greater in those with more severe disease (Ju et al., 2020; Amanat et al., 2020) but are often of low magnitude (Robbiani et al.”
Research works printed but not linked: 1
- Woodruff, 2020, Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation, medRxiv
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Evolution of antibody immunity to SARS-CoV-2
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SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2
Clausen, T. M., Sandoval, D. R., Spliid, C. B., Pihl, J., Perrett, H. R., Painter, C. D., Narayanan, A., Majowicz, S. A., Kwong, E. M., McVicar, R. N., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.033 · Cited by 1,197
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Single-cell multi-omics analysis of the immune response in COVID-19
Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration, Stephenson, E., Reynolds, G., Botting, R. A., Calero-Nieto, F. J., Morgan, M. D., Tuong, Z. K., Bach, K., Sungnak, W., Worlock, K. B., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01329-2 · Cited by 742
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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