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Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19.
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, Mathias; Walker, Bruce D; Yu, Xu G; Padera, Robert F.
  • Kaneko N; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Kuo HH; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Boucau J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Farmer JR; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Allard-Chamard H; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Rheumatology, Faculté de Médecine et des Sciences de la Santé de l'Université de Sherbrooke et Centre de Recherche Clinique Étienne-Le Bel, Sherbrooke, QC J1K 2R1, Canada.
  • Mahajan VS; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Piechocka-Trocha A; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Lefteri K; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Osborn M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Bals J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Bartsch YC; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Bonheur N; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Caradonna TM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Chevalier J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Chowdhury F; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Diefenbach TJ; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Einkauf K; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Fallon J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Feldman J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Finn KK; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Garcia-Broncano P; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Hartana CA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Hauser BM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Jiang C; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Kaplonek P; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Karpell M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Koscher EC; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Lian X; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Liu H; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Liu J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Ly NL; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Michell AR; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Rassadkina Y; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Seiger K; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Sessa L; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Shin S; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Singh N; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Sun W; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Sun X; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Ticheli HJ; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Waring MT; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Zhu AL; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Alter G; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Li JZ; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Lingwood D; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Schmidt AG; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Lichterfeld M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Walker BD; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biology and Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Yu XG; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Padera RF; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: rpadera@bwh.harvard.edu.
Cell ; 183(1): 143-157.e13, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-720447
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / T-Lymphocytes, Helper-Inducer / Coronavirus Infections / Germinal Center Type of study: Etiology study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.08.025

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / T-Lymphocytes, Helper-Inducer / Coronavirus Infections / Germinal Center Type of study: Etiology study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.08.025