B cells in metabolic dysfunction-associated steatotic liver disease (MASLD): From mechanisms to therapeutic...

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 30 % of the global population and has become a major cause of chronic liver disease, encompassing progressive conditions like metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and related hepatocellular carcinoma (HCC). Adaptive immunity, particularly B cells, plays a critical role in MASLD pathogenesis. Different B cell subsets, including B1, B2 cells, and regulatory B cells (Bregs), participate in disease progression through various mechanisms, such as cytokine secretion, antibody production, and crosstalk between adipose tissue and the liver, influencing inflammation, insulin resistance, and fibrosis development. Key factors like B cell-activating factor (BAFF) and signaling pathways including toll-like receptor (TLR) signaling are involved in B cell activation and their pathogenic effects. Emerging therapeutic strategies target B cell migration or signaling pathways. This review summarizes current evidence on B cells' multifaceted roles in MASLD progression, focusing on their activation mechanisms in MASH-related fibrosis and exploring potential B cell-targeted therapeutic prospects.