Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada.
Rosalind & Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Immunol Cell Biol. 2024 Oct;102(9):801-816. doi: 10.1111/imcb.12808. Epub 2024 Jul 15.
Chronic viral infections cause thymic involution yet the potential for broader, longer-term impact on thymic composition remains unexplored. Here we show that chronic, but not acute, lymphocytic choriomeningitis virus infection promotes a unique population of immature B cells in the thymus. We show that chronic viral infection promotes signals within the thymus, including the expression of B-cell activating factor (BAFF), that favor the maturation of this population as these cells acquire expression of CD19 and immunoglobulin M. Mechanistically, type I interferon (IFN-I), predominantly IFNβ, signals to thymic hematopoietic cells, strongly delaying T-cell development at the earliest precursor stage. Furthermore, IFN-I signaling to the nonhematopoietic compartment provides a second signal essential to favor B-cell differentiation and maturation within the thymus. Importantly, chronic infection yields changes in the B-cell population for at least 50 days following infection, long after thymic atrophy has subsided. Thus, the inflammatory milieu induced by chronic viral infection has a profound, and long-lasting, effect on thymic composition leading to the generation of a novel population of thymic B cells.
慢性病毒感染会导致胸腺萎缩，但它对胸腺组成的潜在更广泛、更长期的影响仍未被探索。在这里，我们表明慢性而非急性淋巴细胞脉络丛脑膜炎病毒感染会促进胸腺中独特的不成熟 B 细胞群体的产生。我们表明，慢性病毒感染会促进胸腺内的信号，包括 B 细胞激活因子 (BAFF) 的表达，这有利于这些细胞获得 CD19 和免疫球蛋白 M 的表达，从而促进该群体的成熟。在机制上，I 型干扰素 (IFN-I)，主要是 IFNβ，向胸腺造血细胞发出信号，强烈延迟最早的前体细胞阶段的 T 细胞发育。此外，IFN-I 向非造血区室的信号提供了第二个信号，对于在胸腺内有利于 B 细胞分化和成熟至关重要。重要的是，慢性感染会导致 B 细胞群体发生变化，至少在感染后 50 天内，这一变化持续时间远长于胸腺萎缩。因此，慢性病毒感染引起的炎症环境对胸腺组成产生了深远且持久的影响，导致了新型胸腺 B 细胞群体的产生。
