Author: Kaneko, Naoki; Kuo, Hsiao-Hsuan; Boucau, Julie; Farmer, Jocelyn R.; Allard-Chamard, Hugues; Mahajan, Vinay S.; Piechocka-Trocha, Alicja; Lefteri, Kristina; Osborn, Matthew; Bals, Julia; Bartsch, Yannic C.; Bonheur, Nathalie; Caradonna, Timothy M.; Chevalier, Josh; Chowdhury, Fatema; Diefenbach, Thomas J.; Einkauf, Kevin; Fallon, Jon; Feldman, Jared; Finn, Kelsey K.; Garcia-Broncano, Pilar; Hartana, Ciputra Adijaya; Hauser, Blake M.; Jiang, Chenyang; Kaplonek, Paulina; Karpell, Marshall; Koscher, Eric C.; Lian, Xiaodong; Liu, Hang; Liu, Jinqing; Ly, Ngoc L.; Michell, Ashlin R.; Rassadkina, Yelizaveta; Seiger, Kyra; Sessa, Libera; Shin, Sally; Singh, Nishant; Sun, Weiwei; Sun, Xiaoming; Ticheli, Hannah J.; Waring, Michael T.; Zhu, Alex L.; Alter, Galit; Li, Jonathan Z.; Lingwood, Daniel; Schmidt, Aaron G.; Lichterfeld, Matthias; Walker, Bruce D.; Yu, Xu; Padera, Robert F.; Pillai, Shiv; Abayneh, Betelihem A.; Allen, Patrick; Antille, Diane; Armstrong, Katrina; Balazs, Alejandro; Barbash, Max; Boyce, Siobhan; Braley, Joan; Branch, Karen; Broderick, Katherine; Daley, George; Ellman, Ashley; Fedirko, Liz; Flaherty, Keith; Flannery, Jeanne; Forde, Pamela; Gettings, Elise; Golan, David; Griffin, Amanda; Grimmel, Sheila; Grinke, Kathleen; Hall, Kathryn; Healey, Meg; Heller, Howard; Henault, Deborah; Holland, Grace; Kayitesi, Chantal; Lam, Evan C.; LaValle, Vlasta; Lu, Yuting; Luthern, Sara; Marchewska, Jordan; Martino, Brittni; Millstrom, Ilan; Miranda, Noah; Nambu, Christian; Nelson, Susan; Noone, Marjorie; O’Callaghan, Claire; Ommerborn, Christine; Pacheco, Lois Chris; Phan, Nicole; Porto, Falisha A.; Reissis, Alexandra; Ruzicka, Francis; Ryan, Edward; Selleck, Katheleen; Sharpe, Arlene; Sharr, Christianne; Slaugenhaupt, Sue; Sheppard, Kimberly Smith; Suschana, Elizabeth; Wilson, Vivine; Worrall, Daniel
Title: Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19 Cord-id: 3f0pgo4z Document date: 2020_8_19
ID: 3f0pgo4z
Snippet: 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
Document: 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.
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