Details

Autor(en) / Beteiligte

• Kaneko, Naoki
• Kuo, Hsiao-Hsuan
• Boucau, Julie
• Farmer, Jocelyn R.
• Allard-Chamard, Hugues
• Mahajan, Vinay S.
• Piechocka-Trocha, Alicja
• Lefteri, Kristina
• Osborn, Matthew
• 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.
• Alter, Galit
• Li, Jonathan Z.
• Lingwood, Daniel
• Schmidt, Aaron G.
• Lichterfeld, Mathias
• Walker, Bruce D.
• Yu, Xu G.
• Padera, Robert F.
• Pillai, Shiv

Titel

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

Ist Teil von

• Cell, 2020-10, Vol.183 (1), p.143-157.e13

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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 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. [Display omitted] •Germinal centers are lost in lymph nodes and spleens in acute COVID-19•Bcl-6+ GC B cells and Bcl-6+ T follicular helper cells are markedly diminished•Abundant TH1 cells and aberrant TNF-α production are seen in COVID-19 lymph nodes•SARS-CoV-2-specific activated B cells accumulate in the blood of patients Shiv Pillai and colleagues show that in acute COVID-19, there is a striking loss of germinal centers in lymph nodes and spleens and depletion of Bcl-6+ B cells but preservation of AID+ B cells. A specific block in germinal center type Bcl-6+ T follicular helper cell differentiation may explain the loss of germinal centers and the accumulation of non-germinal-center-derived activated B cells. These data suggest an underlying basis for the lower quality and lack of durability of humoral immune responses observed during natural infection with SARS-CoV-2 and have significant implications for expectations of herd immunity.