N. Kaneko, H. Kuo, J. Boucau, J. Farmer, H. Allard-Chamard, V. Mahajan, A. Piechocka-Trocha, K. Lefteri, Matt Osborn, Julia Bals, Yannic C. Bartsch, Nathalie Bonheur, T. Caradonna, Joshua M Chevalier, Fatema Z Chowdhury, T. Diefenbach, Kevin B Einkauf, Jonathan K. Fallon, J. Feldman, Kelsey K. Finn, Pilar García-Broncano, C. Hartana, B. Hauser, Chenyan Jiang, P. Kaplonek, Marshall Karpell, Eric C. Koscher, Xiaodong Lian, Hang Liu, Jinqing Liu, Ngoc L. Ly, Ashlin Michell, Yelizaveta Rassadkina, Kyra Seiger, Libera Sessa, Sally A Shin, N. Singh, Weiwei Sun, Xiaoming Sun, Hannah J. Ticheli, M. Waring, A. Zhu, G. Alter, Jonathan Z. Li, D. Lingwood, A. Schmidt, M. Lichterfeld, B. Walker, Xu G. Yu, R. Padera, S. Pillai
Cell, 2020
Summary Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers, 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.
Cited by 206 publications.
Field of study: Biology