VPREB1

VpreB1 (Pre-B lymphocyte protein 1), encoded by the VPREB1 gene, is a critical component of the surrogate light chain (SLC) complex in B-cell development. It pairs with λ5 (IGLL1) to form the SLC, which combines with the immunoglobulin heavy chain (μ chain) to assemble the pre-B cell receptor (pre-BCR). This receptor mediates signaling for clonal expansion and allelic exclusion during early B-cell maturation in the bone marrow. The pre-BCR activates pathways including SYK, BTK, and PI3K/AKT, ensuring proper B-cell lineage progression. Dysregulation of VPREB1 is linked to primary immunodeficiencies like agammaglobulinemia and B-cell acute lymphoblastic leukemia (B-ALL), where aberrant pre-BCR signaling drives malignant transformation. While no direct VPREB1-targeted therapies exist, drugs modulating downstream kinases (e.g., ibrutinib targeting BTK) show efficacy in B-cell malignancies. Recent studies explore monoclonal antibodies against the SLC complex as potential therapeutic strategies.