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

被引：226

作者：

Kaneko, Naoki ^{[1
]}

Kuo, Hsiao-Hsuan ^{[1
]}

Boucau, Julie ^{[1
]}

Farmer, Jocelyn R. ^{[1
]}

Allard-Chamard, Hugues ^{[1
,4
,5
]}

Mahajan, Vinay S. ^{[1
,2
]}

Piechocka-Trocha, Alicja ^{[1
,7
]}

Lefteri, Kristina ^{[1
]}

Osborn, Matthew ^{[1
]}

Bals, Julia ^{[1
]}

Bartsch, Yannic C. ^{[1
]}

Bonheur, Nathalie ^{[1
]}

Caradonna, Timothy M. ^{[1
]}

Chevalier, Josh ^{[1
]}

Chowdhury, Fatema ^{[1
]}

Diefenbach, Thomas J. ^{[1
]}

Einkauf, Kevin ^{[1
]}

Fallon, Jon ^{[1
]}

Feldman, Jared ^{[1
]}

Finn, Kelsey K. ^{[1
]}

Garcia-Broncano, Pilar ^{[1
]}

Hartana, Ciputra Adijaya ^{[1
]}

Hauser, Blake M. ^{[1
]}

Jiang, Chenyang ^{[1
]}

Kaplonek, Paulina ^{[1
]}

Karpell, Marshall ^{[1
]}

Koscher, Eric C. ^{[1
]}

Lian, Xiaodong ^{[1
]}

Liu, Hang ^{[1
]}

Liu, Jinqing ^{[1
]}

Ly, Ngoc L. ^{[1
]}

Michell, Ashlin R. ^{[1
]}

Rassadkina, Yelizaveta ^{[1
]}

Seiger, Kyra ^{[1
]}

Sessa, Libera ^{[1
]}

Shin, Sally ^{[1
]}

Singh, Nishant ^{[1
]}

Sun, Weiwei ^{[1
]}

Sun, Xiaoming ^{[1
]}

Ticheli, Hannah J. ^{[1
]}

Waring, Michael T. ^{[1
,7
]}

Zhu, Alex L. ^{[1
]}

Alter, Galit ^{[1
]}

Li, Jonathan Z. ^{[3
]}

Lingwood, Daniel ^{[1
]}

Schmidt, Aaron G. ^{[1
,6
]}

Lichterfeld, Mathias ^{[1
,3
]}

Walker, Bruce D. ^{[1
,7
,8
,9
]}

Yu, Xu G. ^{[1
,3
]}

Padera, Robert F., Jr. ^{[2
]}

机构：

[1] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[2] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[4] Univ Sherbrooke &, Fac Med & Sci Sante, Div Rheumatol, Sherbrooke, PQ J1K 2R1, Canada

[5] Ctr Rech Clin Etienne Le Bel, Sherbrooke, PQ J1K 2R1, Canada

[6] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA

[7] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[8] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[9] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA

来源：

CELL | 2020年 / 183卷 / 01期

关键词：

CENTER B-CELL; CLINICAL CHARACTERISTICS; DISEASE; 2019; CORONAVIRUS; RESPONSES; PATHOGENESIS; INFECTIONS; PATHOLOGY; TISSUE; ROLES;

D O I：

10.1016/j.cell.2020.08.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 B cells. Absence of germinal centers correlated with an early specific block in Bcl-6 T-FH cell differentiation together with an increase in T-bet(+) T-H1 cells and aberrant extra-follicular TNF-alpha 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(+) T-FH 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.

引用

页码：143 / +

页数：28

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