Type I interferon induced during chronic viral infection favors B‐cell development in the thymus

Abstract

AbstractChronic 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.