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⁺ T_FH cell differentiation together with an increase in T-bet⁺ T_H1 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⁺ T_FH 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.

与其他人类冠状病毒流行病一样，2019 年冠状病毒病 (COVID-19) 的体液反应通常具有有限的持久性。为了解决潜在的病因，我们检查了急性 SARS-CoV-2 感染中的死后胸部淋巴结和脾脏，观察到生发中心缺失和 Bcl-6 ^{+生发中心 B 细胞显着减少，但 AID +} B 细胞保留. 生发中心的缺失与 Bcl-6 ⁺ T _FH细胞分化的早期特异性阻滞以及 T-bet ⁺ T _{H1的增加相关}细胞和异常的滤泡外 TNF-α 积累。平行的外周血研究显示，严重疾病中移行和滤泡 B 细胞的丢失以及 SARS-CoV-2 特异性“疾病相关”B 细胞群的积累。这些数据确定了 COVID-19 疾病早期 Bcl-6 ⁺ T _FH细胞生成缺陷和体液免疫诱导失调，为冠状病毒感染中抗体反应的有限持久性提供了机制解释，并表明通过自然感染实现群体免疫可能是难的。