美国哈佛大学Christian Nambu、Robert F. Padera Jr.等研究人员合作发现，COVID-19患者中存在表达Bcl-6的T滤泡辅助细胞（TFH）和生发中心的丢失。相关论文于2020年8月19日在线发表在《细胞》杂志上。

研究人员表示，正如其他人类冠状病毒的流行一样，COVID-19疾病的体液反应通常存在有限的持久性。

为了解决潜在的病因，研究人员检查了急性SARS-CoV-2感染后死者的胸淋巴结和脾脏，并观察到生发中心缺失、Bcl-6⁺生发中心B细胞显著减少，但AID⁺B细胞得以保存。生发中心的缺乏与Bcl-6⁺TFH细胞分化的早期特异性阻断以及T-bet⁺TH1细胞的增加和小泡状细胞外TNF-α的积累有关。外周血研究显示，严重疾病中过渡性B和滤泡性B细胞的丢失以及SARS-CoV-2特异性“疾病相关” B细胞群体的积累。

这些数据在COVID-19疾病早期发现了缺陷的Bcl-6⁺TFH细胞生成和体液免疫诱导失调，从而为冠状病毒感染中抗体应答的有限持久性提供了机制解释，并暗示通过自然感染实现群体免疫可能很困难。

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