草鱼外周血IgM<sup>+</sup> B细胞的单细胞图谱为揭示硬骨鱼类B细胞介导的免疫应答提供新见解

Teleost peripheral blood contains a remarkably high proportion of B cells, accounting for 15%-50% of circulating lymphocytes. However, their immune responses to bacterial infection are yet to be elucidated. In the present study, 10× Genomics single-cell RNA sequencing (scRNA-seq) was employed to characterize the transcriptomic landscape of peripheral blood IgM ⁺ B cells in grass carp ( <i>Ctenopharyngodon idella</i>) following challenge with <i>Aeromonas hydrophila</i>, a major aquatic pathogen. Six transcriptionally distinct IgM ⁺ B cell subpopulations were identified, including (im)mature B cells, innate B cells, proliferating B cells, IgD ^high B cells, and two infection-induced subsets denoted as infection Ⅰ and Ⅱ B cells. Bacterial infection altered the cellular heterogeneity of IgM ⁺ B cells, triggered metabolic reprogramming in (im)mature and innate B cell subpopulations, and enhanced the immunological activation of circulating B cells. Notably, infection Ⅰ B cells demonstrated robust induction of interferon φ1 ( <i>IFNφ1</i>), a type I IFN, following <i>A. hydrophila</i> exposure. This induction was further validated through <i>in vitro</i> bacterial stimulation, indicating that teleost B cells actively contribute to innate antibacterial responses through IFN signaling. Additionally, the IgD ^high B cell subpopulation remained consistently present in peripheral blood across both infected and uninfected states, pointing to a constitutive and likely mature phenotype. These findings significantly advance our understanding of the heterogeneity of peripheral blood IgM ⁺ B cells and provide new insights into IgM ⁺ B cell-mediated immune responses in teleost fish.