TY - JOUR
T1 - Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19
AU - the Massachusetts Consortium on Pathogen Readiness Specimen Working Group
AU - Kaneko, Naoki
AU - Kuo, Hsiao Hsuan
AU - Boucau, Julie
AU - Farmer, Jocelyn R.
AU - Allard-Chamard, Hugues
AU - Mahajan, Vinay S.
AU - Piechocka-Trocha, Alicja
AU - Lefteri, Kristina
AU - Osborn, Matthew
AU - Bals, Julia
AU - Bartsch, Yannic C.
AU - Bonheur, Nathalie
AU - Caradonna, Timothy M.
AU - Chevalier, Josh
AU - Chowdhury, Fatema
AU - Diefenbach, Thomas J.
AU - Einkauf, Kevin
AU - Fallon, Jon
AU - Feldman, Jared
AU - Finn, Kelsey K.
AU - Garcia-Broncano, Pilar
AU - Hartana, Ciputra Adijaya
AU - Hauser, Blake M.
AU - Jiang, Chenyang
AU - Kaplonek, Paulina
AU - Karpell, Marshall
AU - Koscher, Eric C.
AU - Lian, Xiaodong
AU - Liu, Hang
AU - Liu, Jinqing
AU - Ly, Ngoc L.
AU - Michell, Ashlin R.
AU - Rassadkina, Yelizaveta
AU - Seiger, Kyra
AU - Sessa, Libera
AU - Shin, Sally
AU - Singh, Nishant
AU - Sun, Weiwei
AU - Sun, Xiaoming
AU - Ticheli, Hannah J.
AU - Waring, Michael T.
AU - Zhu, Alex L.
AU - Alter, Galit
AU - Li, Jonathan Z.
AU - Lingwood, Daniel
AU - Schmidt, Aaron G.
AU - Lichterfeld, Mathias
AU - Walker, Bruce D.
AU - Yu, Xu G.
AU - Padera, Robert F.
N1 - Funding Information:
We thank Doug Kwon and Brooke Spencer of the Ragon Institute for access to Ragon Institute Tissue core specimens and Andrew Lichtman of BWH Pathology for helpful advice. This work was supported by NIH U19 AI110495 to S.P., NIH R01 AI146779 to A.G.S., and NIH R01AI137057 and DP2DA042422 to D.L. B.M.H. was supported by NIGMS T32 GM007753 and T.M.C. was supported by T32 AI007245 . Funding for these studies from the Massachusetts Consortium of Pathogen Readiness , the Mark and Lisa Schwartz Foundation , and Enid Schwartz is also acknowledged. The graphical abstract was prepared using Biorender.
Funding Information:
We thank Doug Kwon and Brooke Spencer of the Ragon Institute for access to Ragon Institute Tissue core specimens and Andrew Lichtman of BWH Pathology for helpful advice. This work was supported by NIH U19 AI110495 to S.P. NIH R01 AI146779 to A.G.S. and NIH R01AI137057 and DP2DA042422 to D.L. B.M.H. was supported by NIGMS T32 GM007753 and T.M.C. was supported by T32 AI007245. Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation, and Enid Schwartz is also acknowledged. The graphical abstract was prepared using Biorender. Conceptualization, S.P. R.F.P. N.K. J.R.F. H.-H.K. J. Boucau, B.D.W. and X.G.Y.; Methodology, H.A.-C. N.K. J.R.F. T.J.D. M.T.W. H.-H.K. and J. Boucau; Investigation, N.K. H.-H.K. J. Boucau, A.P.-T. K.L. M.O. J. Bals, Y.C.B. N.B. J.C. F.C. K.E. J. Fallon, K.K.F. P.G.-B. C.A.H. C.J. P.K. M.K. X.L. H.L. J.L. N.L.L. A.R.M. Y.R. K.S. L.S. S.S. N.S. W.S. X.S. H.J.T. A.L.Z. and R.F.P.; Resources, R.F.P. B.D.W. X.G,Y. J.L. V.S.M. D.L. A.G.S. B.M.H. J. Feldman, T.M.C. J. Bals, G.A. and M.L.; Original Draft, S.P. N.K. J.R.F. J. Boucau, and H.-H.K.; Review/Editing, S.P. B.D.W. N.K. J.R.F. H.-H.K. J. Boucau, and H.A.-C.; Supervision, S.P. and X.G.Y. S.P. is on the SAB of Abpro Inc. and Pulsar Biopharma. G.A. is founder of Seromyx Systems Inc.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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+ TFH cell differentiation together with an increase in T-bet+ TH1 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+ TFH 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.
AB - 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+ TFH cell differentiation together with an increase in T-bet+ TH1 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+ TFH 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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U2 - 10.1016/j.cell.2020.08.025
DO - 10.1016/j.cell.2020.08.025
M3 - Article
C2 - 32877699
AN - SCOPUS:85090137765
SN - 0092-8674
VL - 183
SP - 143-157.e13
JO - Cell
JF - Cell
IS - 1
ER -
