CD19 is a B-cell surface coreceptor that plays a critical role in humoral immunity. As a BCR complex coreceptor, CD19 functions to lower the threshold for B-cell activation and amplify downstream signaling pathways, including phosphatidylinositol 3-kinase activation and intracellular calcium mobilization 123. CD19 is essential for normal B-cell differentiation, proliferation in response to antigens, and generation of high-affinity antibodies and robust serum immunoglobulin levels 43. Notably, CD19 is dispensable for early bone marrow B-cell development 5. Clinically, CD19 loss-of-function mutations cause common variable immunodeficiency type 3, highlighting its importance in adaptive immunity. CD19's prominence on B-cell malignancies has made it a major immunotherapeutic target. CD19-targeted CAR-T cells and bispecific T-cell engagers achieve complete remissions in B-cell acute lymphoblastic leukemia 67. However, antigen escape through CD19 downregulation or loss is a significant resistance mechanism, with transcriptional and post-transcriptional regulators like NUDT21 controlling CD19 expression levels 8. Clinical efficacy correlates with CD19 density on target cells, and therapeutic approaches optimizing CD19 binding affinity and immunogenicity are under active development 910.