Functional remodeling of IgM⁺ B cells in Streptococcus agalactiae-resistant Nile tilapia

Streptococcus agalactiae infection remains a major constraint on the productivity of Nile tilapia (Oreochromis niloticus), a species of considerable economic importance in global aquaculture. Although selective breeding programs have successfully produced tilapia strains with enhanced resistance to this pathogen, the B cell-mediated immune mechanisms underlying this resistance remain unclear. In this study, we systematically investigated differences in IgM ⁺ B cell-mediated immune responses between S. agalactiae-resistant and -susceptible Nile tilapia. Transcriptomic analysis of splenic leukocytes revealed that genes associated with immunoglobulin production and B cell differentiation were markedly upregulated in resistant tilapia following infection. Consistent with these findings, flow cytometry further demonstrated a more pronounced expansion of splenic IgM⁺ B cells in resistant tilapia, which was primarily driven by significantly increased proliferative activity. Importantly, this expansion coincided with elevated activation-induced apoptosis, suggesting accelerated B cell turnover that could facilitate the selection and maintenance of functionally competent cells during the immune response. Functionally, IgM⁺ B cells from resistant tilapia exhibited sustained enhancement of antigen processing capacity following infection. Meanwhile, macrophage-mediated phagocytosis of S. agalactiae increased progressively and became particularly evident at later stages of infection. Moreover, IgM⁺ B cells in resistant tilapia maintained relatively stable intracellular ROS levels, whereas susceptible tilapia exhibited persistent oxidative stress. Collectively, these findings indicate that resistance to S. agalactiae infection in Nile tilapia is closely associated with coordinated functional remodeling of IgM ⁺ B cells, characterized by efficient proliferation, functional maturation, and stringent homeostatic regulation. This refined B cell-mediated immunity likely contributes to effective pathogen clearance and provides an immunological basis for the evaluation and selective breeding of disease-resistant tilapia strains.