Objective：
Acute pancreatitis (AP) is a life-threatening inflammatory disorder with limited therapeutic options, often progressing to systemic complications. While dysregulated immune responses are implicated in AP pathogenesis, the role of adaptive immunity, particularly B-cell-mediated mechanisms, remains poorly understood. This study investigates the regulatory function of marginal zone B and B1 cell-specific protein (MZB1) in AP progression.
Methods：
Peripheral blood mononuclear cells (PBMCs) from AP patients (mild, moderately severe, and severe cases) and healthy controls underwent single-cell RNA sequencing (scRNA-seq). Pancreatic tissues from cerulein-induced AP mouse models (wild-type and Mzb1-/-) were analyzed via bulk RNA sequencing, immunohistochemistry, flow cytometry, and ELISA. Functional assays included Western blotting, immunofluorescence, and chemotaxis evaluation.
Results：
In this study, we revealed the critical role of MZB1 in modulating adaptive immunity during AP based on scRNA-seq and AP mice model. revealed dynamic plasma cell proportions, decreasing in early AP and rebounding during recovery, paralleling MZB1 expression trends. Mzb1-/- mice exhibited exacerbated pancreatic injury, impaired plasma cell maturation, and reduced immunoglobulin secretion. MZB1 deficiency enhanced neutrophil and macrophage chemotaxis via upregulated CXCL13 and CCL2, correlating with heightened immune cell infiltration. Pancreatic enzyme levels and pro-inflammatory cytokines were elevated in Mzb1-/- mice.
Conclusion：
MZB1 modulates AP progression by regulating plasma cells function and restraining excessive immune cell chemotaxis. Its deficiency exacerbates pancreatic inflammation through impaired adaptive immunity and amplified innate immune responses. These findings highlight MZB1 as a potential therapeutic target for mitigating AP severity.