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The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of 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, Matt; 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; Li, Jonathan; Lingwood, Daniel; Schmidt, Aaron G; Lichterfeld, Matthias; Walker, Bruce D; Yu, Xu; Padera, Robert F; Pillai, Shiv.
Afiliação
  • 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.
  • Mahajan VS; 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, Québec, J1K 2R1, Canada.
  • Piechocka-Trocha A; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Lefteri K; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
  • Osborn M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Bals J; Howard Hughes Medical Institute, Chevy Chase MD, 20815.
  • 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.
  • Zhu AL; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Li J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Lingwood D; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Schmidt AG; Howard Hughes Medical Institute, Chevy Chase MD, 20815.
  • Lichterfeld M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Walker BD; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
  • Yu X; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Padera RF; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Pillai S; Department of Microbiology, Harvard Medical School, Boston, MA 02115.
SSRN ; : 3652322, 2020 Jul 16.
Article em En | MEDLINE | ID: mdl-32742244
ABSTRACT
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-a 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.

Funding:

This work was supported by NIH U19 AI110495 to SP, NIH R01 AI146779 to AGS, NIH R01AI137057 and DP2DA042422 to DL, BMH was supported by NIGMS T32 GM007753, TMC 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. Conflict of Interest None. Ethical Approval This study was performed with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women's Hospital.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: SSRN Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: SSRN Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos