COVID-19患者出現T濾泡輔助細胞和生發中心的丟失

COVID-19患者出現T濾泡輔助細胞和生發中心的丟失

作者：

小柯機器人

發布時間：2020/8/21 15:57:05

美國哈佛大學Christian Nambu、Robert F. Padera Jr.等研究人員合作發現，COVID-19患者中存在表達Bcl-6的T濾泡輔助細胞（TFH）和生發中心的丟失。相關論文於2020年8月19日在線發表在《細胞》雜誌上。

研究人員表示，正如其他人類冠狀病毒的流行一樣，COVID-19疾病的體液反應通常存在有限的持久性。

為了解決潛在的病因，研究人員檢查了急性SARS-CoV-2感染後死者的胸淋巴結和脾臟，並觀察到生發中心缺失、Bcl-6⁺生發中心B細胞顯著減少，但AID⁺B細胞得以保存。生發中心的缺乏與Bcl-6⁺TFH細胞分化的早期特異性阻斷以及T-bet⁺TH1細胞的增加和小泡狀細胞外TNF-α的積累有關。外周血研究顯示，嚴重疾病中過渡性B和濾泡性B細胞的丟失以及SARS-CoV-2特異性「疾病相關」 B細胞群體的積累。

這些數據在COVID-19疾病早期發現了缺陷的Bcl-6⁺TFH細胞生成和體液免疫誘導失調，從而為冠狀病毒感染中抗體應答的有限持久性提供了機制解釋，並暗示通過自然感染實現群體免疫可能很困難。

附：英文原文

Title: Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19

Author: Naoki Kaneko, Hsiao-Hsuan Kuo, Julie Boucau, Jocelyn R. Farmer, Hugues Allard-Chamard, Vinay S. Mahajan, Alicja Piechocka-Trocha, Kristina Lefteri, Matthew Osborn, Julia Bals, Yannic C. Bartsch, Nathalie Bonheur, Timothy M. Caradonna, Josh Chevalier, Fatema Chowdhury, Thomas J. Diefenbach, Kevin Einkauf, Jon Fallon, Jared Feldman, Kelsey K. Finn, Pilar Garcia-Broncano, Ciputra Adijaya Hartana, Blake M. Hauser, Chenyang Jiang, Paulina Kaplonek, Marshall Karpell, Eric C. Koscher, Xiaodong Lian, Hang Liu, Jinqing Liu, Ngoc L. Ly, Ashlin R. Michell, Yelizaveta Rassadkina, Kyra Seiger, Libera Sessa, Sally Shin, Nishant Singh, Weiwei Sun, Xiaoming Sun, Hannah J. Ticheli, Michael T. Waring, Alex L. Zhu, Galit Alter, Jonathan Z. Li, Daniel Lingwood, Aaron G. Schmidt, Matthias Lichterfeld, Bruce D. Walker, Xu Yu, Robert F. Padera, Shiv Pillai, Betelihem A. Abayneh, Patrick Allen, Diane Antille, Katrina Armstrong, Alejandro Balazs, Max Barbash, Siobhan Boyce, Joan Braley, Karen Branch, Katherine Broderick, George Daley, Ashley Ellman, Liz Fedirko, Keith Flaherty, Jeanne Flannery, Pamela Forde, Elise Gettings, David Golan, Amanda Griffin, Sheila Grimmel, Kathleen Grinke, Kathryn Hall, Meg Healey, Howard Heller, Deborah Henault, Grace Holland, Chantal Kayitesi, Evan C. Lam, Vlasta LaValle, Yuting Lu, Sara Luthern, Jordan Marchewska, Brittni Martino, Ilan Millstrom, Noah Miranda, Christian Nambu

Issue&Volume:

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-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.

DOI: 10.1016/j.cell.2020.08.025

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31067-9

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