The bursa of Fabricius, the key humoral immune organ unique to birds, is critical for B cell differentiation and antibody production. BP8 (AGHTKKAP) is a novel immunomodulatory peptide that regulates B-cell development. Gene microarray was used to investigate the mechanism of BP8 on B cell development. BP8 regulated expressions of 1,570 genes that were involved in retinol metabolism, the Wnt signaling pathway, MAPK pathway, Jak-Stat pathway, Notch signaling pathway, cytokine-cytokine receptor interaction, and Ca2+ signals. Finally, BP8 triggered ADH7 and RDH10 expression, interacted with retinol binding protein, and regulated retinol uptake in vitro and vivo. These data reveal a bursal-derived multifunctional factor, BP8, as a novel biomaterial which is essential for the development of the immune system and represents an important linker between the B cell development and retinol metabolism. This study elucidates the mechanisms involved in humoral immune system and has implications in treating human diseases.