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

By N. Kaneko, H. Kuo, J. Boucau, Jocelyn R. Farmer, Hugues Allard-Chamard, V. Mahajan, A. Piechocka-Trocha, Kristina Lefteri, Matt Osborn, Julia Bals and 41 more. Cell, 2020

657 citations recorded by the source corpus.

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.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/1ccc2e6c54ba3f410d5f24b69dbbb653565d5a0d

Citations in the corpus

• Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes (2020, neutral): “Post-mortem examination of spleens and lymph nodes from patients with COVID-19 has revealed the lack of germinal centers, an essential part that can create a high-quality antibody response to produce long-term immunity (Kaneko et al., 2020).”