Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19.
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+
cell differentiation together with an increase in T-bet+
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+
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.
Kaneko, N; Kuo, H-H; Boucau, J; Farmer, JR; Allard-Chamard, H; Mahajan, VS; Piechocka-Trocha, A; Lefteri, K; Osborn, M; Bals, J; Bartsch, YC; Bonheur, N; Caradonna, TM; Chevalier, J; Chowdhury, F; Diefenbach, TJ; Einkauf, K; Fallon, J; Feldman, J; Finn, KK; Garcia-Broncano, P; Hartana, CA; Hauser, BM; Jiang, C; Kaplonek, P; Karpell, M; Koscher, EC; Lian, X; Liu, H; Liu, J; Ly, NL; Michell, AR; Rassadkina, Y; Seiger, K; Sessa, L; Shin, S; Singh, N; Sun, W; Sun, X; Ticheli, HJ; Waring, MT; Zhu, AL; Alter, G; Li, JZ; Lingwood, D; Schmidt, AG; Lichterfeld, M; Walker, BD; Yu, XG; Padera, RF; Pillai, S; Massachusetts Consortium on Pathogen Readiness Specimen Working Group,
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