tetano
Editor, Senior Moderator
Cell
. 2020 Aug 19;S0092-8674(20)31067-9.
doi: 10.1016/j.cell.2020.08.025. Online ahead of print.
Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19
Naoki Kaneko[SUP] 1 [/SUP], Hsiao-Hsuan Kuo[SUP] 1 [/SUP], Julie Boucau[SUP] 1 [/SUP], Jocelyn R Farmer[SUP] 1 [/SUP], Hugues Allard-Chamard[SUP] 2 [/SUP], Vinay S Mahajan[SUP] 3 [/SUP], Alicja Piechocka-Trocha[SUP] 4 [/SUP], Kristina Lefteri[SUP] 1 [/SUP], Matthew Osborn[SUP] 1 [/SUP], Julia Bals[SUP] 1 [/SUP], Yannic C Bartsch[SUP] 1 [/SUP], Nathalie Bonheur[SUP] 1 [/SUP], Timothy M Caradonna[SUP] 1 [/SUP], Josh Chevalier[SUP] 1 [/SUP], Fatema Chowdhury[SUP] 1 [/SUP], Thomas J Diefenbach[SUP] 1 [/SUP], Kevin Einkauf[SUP] 1 [/SUP], Jon Fallon[SUP] 1 [/SUP], Jared Feldman[SUP] 1 [/SUP], Kelsey K Finn[SUP] 1 [/SUP], Pilar Garcia-Broncano[SUP] 1 [/SUP], Ciputra Adijaya Hartana[SUP] 1 [/SUP], Blake M Hauser[SUP] 1 [/SUP], Chenyang Jiang[SUP] 1 [/SUP], Paulina Kaplonek[SUP] 1 [/SUP], Marshall Karpell[SUP] 1 [/SUP], Eric C Koscher[SUP] 1 [/SUP], Xiaodong Lian[SUP] 1 [/SUP], Hang Liu[SUP] 1 [/SUP], Jinqing Liu[SUP] 1 [/SUP], Ngoc L Ly[SUP] 1 [/SUP], Ashlin R Michell[SUP] 1 [/SUP], Yelizaveta Rassadkina[SUP] 1 [/SUP], Kyra Seiger[SUP] 1 [/SUP], Libera Sessa[SUP] 1 [/SUP], Sally Shin[SUP] 1 [/SUP], Nishant Singh[SUP] 1 [/SUP], Weiwei Sun[SUP] 1 [/SUP], Xiaoming Sun[SUP] 1 [/SUP], Hannah J Ticheli[SUP] 1 [/SUP], Michael T Waring[SUP] 4 [/SUP], Alex L Zhu[SUP] 1 [/SUP], Galit Alter[SUP] 1 [/SUP], Jonathan Z Li[SUP] 5 [/SUP], Daniel Lingwood[SUP] 1 [/SUP], Aaron G Schmidt[SUP] 6 [/SUP], Mathias Lichterfeld[SUP] 7 [/SUP], Bruce D Walker[SUP] 8 [/SUP], Xu G Yu[SUP] 7 [/SUP], Robert F Padera Jr[SUP] 9 [/SUP], Shiv Pillai[SUP] 10 [/SUP], Massachusetts Consortium on Pathogen Readiness Specimen Working Group
Affiliations
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[SUP]+[/SUP] germinal center B cells but preservation of AID[SUP]+[/SUP] B cells. Absence of germinal centers correlated with an early specific block in Bcl-6[SUP]+[/SUP] T[SUB]FH[/SUB] cell differentiation together with an increase in T-bet[SUP]+[/SUP] T[SUB]H1[/SUB] 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[SUP]+[/SUP] T[SUB]FH[/SUB] 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.
Keywords: COVID-19; SARS-CoV-2; T follicular helper cells; TNF-α; cytokine dysregulation; double-negative B cells; extra-follicular B cells; germinal centers; humoral immunity; plasmablasts.
. 2020 Aug 19;S0092-8674(20)31067-9.
doi: 10.1016/j.cell.2020.08.025. Online ahead of print.
Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19
Naoki Kaneko[SUP] 1 [/SUP], Hsiao-Hsuan Kuo[SUP] 1 [/SUP], Julie Boucau[SUP] 1 [/SUP], Jocelyn R Farmer[SUP] 1 [/SUP], Hugues Allard-Chamard[SUP] 2 [/SUP], Vinay S Mahajan[SUP] 3 [/SUP], Alicja Piechocka-Trocha[SUP] 4 [/SUP], Kristina Lefteri[SUP] 1 [/SUP], Matthew Osborn[SUP] 1 [/SUP], Julia Bals[SUP] 1 [/SUP], Yannic C Bartsch[SUP] 1 [/SUP], Nathalie Bonheur[SUP] 1 [/SUP], Timothy M Caradonna[SUP] 1 [/SUP], Josh Chevalier[SUP] 1 [/SUP], Fatema Chowdhury[SUP] 1 [/SUP], Thomas J Diefenbach[SUP] 1 [/SUP], Kevin Einkauf[SUP] 1 [/SUP], Jon Fallon[SUP] 1 [/SUP], Jared Feldman[SUP] 1 [/SUP], Kelsey K Finn[SUP] 1 [/SUP], Pilar Garcia-Broncano[SUP] 1 [/SUP], Ciputra Adijaya Hartana[SUP] 1 [/SUP], Blake M Hauser[SUP] 1 [/SUP], Chenyang Jiang[SUP] 1 [/SUP], Paulina Kaplonek[SUP] 1 [/SUP], Marshall Karpell[SUP] 1 [/SUP], Eric C Koscher[SUP] 1 [/SUP], Xiaodong Lian[SUP] 1 [/SUP], Hang Liu[SUP] 1 [/SUP], Jinqing Liu[SUP] 1 [/SUP], Ngoc L Ly[SUP] 1 [/SUP], Ashlin R Michell[SUP] 1 [/SUP], Yelizaveta Rassadkina[SUP] 1 [/SUP], Kyra Seiger[SUP] 1 [/SUP], Libera Sessa[SUP] 1 [/SUP], Sally Shin[SUP] 1 [/SUP], Nishant Singh[SUP] 1 [/SUP], Weiwei Sun[SUP] 1 [/SUP], Xiaoming Sun[SUP] 1 [/SUP], Hannah J Ticheli[SUP] 1 [/SUP], Michael T Waring[SUP] 4 [/SUP], Alex L Zhu[SUP] 1 [/SUP], Galit Alter[SUP] 1 [/SUP], Jonathan Z Li[SUP] 5 [/SUP], Daniel Lingwood[SUP] 1 [/SUP], Aaron G Schmidt[SUP] 6 [/SUP], Mathias Lichterfeld[SUP] 7 [/SUP], Bruce D Walker[SUP] 8 [/SUP], Xu G Yu[SUP] 7 [/SUP], Robert F Padera Jr[SUP] 9 [/SUP], Shiv Pillai[SUP] 10 [/SUP], Massachusetts Consortium on Pathogen Readiness Specimen Working Group
Affiliations
- PMID: 32877699
- DOI: 10.1016/j.cell.2020.08.025
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[SUP]+[/SUP] germinal center B cells but preservation of AID[SUP]+[/SUP] B cells. Absence of germinal centers correlated with an early specific block in Bcl-6[SUP]+[/SUP] T[SUB]FH[/SUB] cell differentiation together with an increase in T-bet[SUP]+[/SUP] T[SUB]H1[/SUB] 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[SUP]+[/SUP] T[SUB]FH[/SUB] 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.
Keywords: COVID-19; SARS-CoV-2; T follicular helper cells; TNF-α; cytokine dysregulation; double-negative B cells; extra-follicular B cells; germinal centers; humoral immunity; plasmablasts.