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 as the main cytokines produced and some TNFα as well.
“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]
Studies consistently report defective germinal center responses in secondary lymphoid organs of patients who died from SARS-CoV-2.
“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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- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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