EpCAM (CD326) is dispensable for in vitro B cell activation and maintenance of antibody-secreting cells

Antibody-secreting cells (ASCs) provide the foundation for protective humoral immunity following infection or vaccination. Recent advances have revealed substantial phenotypic complexity within the ASC compartment, associated with diverse functional states and differentiation stages. Epithelial cell adhesion molecule (EpCAM, CD326) has emerged as a marker of mature plasma cells. However, the functional significance of EpCAM in B cells and ASCs remains unclear. Here, we performed an extensive analysis of EpCAM expression throughout the murine B cell lineage, revealing notable EpCAM expression in marginal zone and B1 B cells, with a progressive and significant increase during maturation of ASCs. Following activation in vitro, EpCAM exhibited biphasic induction dynamics, with early and rapid upregulation in response to B cell receptor stimulation and a delayed but sustained expression during plasmablast differentiation. To define EpCAM's functional relevance, we generated B cell-specific EpCAM knock-out mice. Remarkably, deletion of EpCAM did not alter B cell activation, proliferation, or differentiation into plasmablasts in vitro. Moreover, EpCAM-deficient mice showed normal numbers and distributions of B cell subsets and ASCs, along with unchanged serum immunoglobulin abundances. Thus, despite its dynamic regulation and restricted expression pattern, EpCAM is dispensable for B cell activation, ASC differentiation, and maintenance of ASC populations.