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Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19

2020; Cell Press; Volume: 183; Issue: 1 Linguagem: Inglês

10.1016/j.cell.2020.08.025

1097-4172

Naoki Kaneko, Hsiao-Hsuan Kuo, Julie Boucau, Jocelyn R. Farmer, Hugues Allard‐Chamard, Vinay S. Mahajan, Alicja Piechocka‐Trocha, Kristina Lefteri, Matthew R. Osborn, Julia Bals, Yannic C. Bartsch, Nathalie Bonheur, Timothy M. Caradonna, Josh Chevalier, Fatema Z. Chowdhury, Thomas Diefenbach, Kevin Einkauf, Jon Fallon, Jared Feldman, Kelsey Finn, Pilar García‐Broncano, Ciputra Adijaya Hartana, Blake M. Hauser, Chenyang Jiang, Paulina Kapłonek, Marshall Karpell, Eric C. Koscher, Xiaodong Lian, Hang Liu, Jin-Qing Liu, Ngoc L. Ly, Ashlin R. Michell, Yelizaveta Rassadkina, Kyra Seiger, Libera Sessa, Sally Shin, Nishant K. Singh, Weiwei Sun, Xiaoming Sun, Hannah Ticheli, Michael T. Waring, Alex Zhu, Galit Alter, Jonathan Z. Li, Daniel Lingwood, Aaron G. Schmidt, Mathias Lichterfeld, Bruce D. Walker, Xu G. Yu, Robert F. Padera, Shiv Pillai,

COVID-19 Clinical Research Studies

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.