Postnatal liver B cell precursors contribute to the establishment of a mature B cell pool in secondary lymphoid organs in mice.

The liver contains a diverse repertoire of leukocytes, with liver B cells representing a significant population of hepatic immune cells in both newborns and adults. Despite their importance, these cells remain largely unexplored. In this study, we comprehensively characterized liver B cells from newborns through adulthood in both humans and mice applying a combination of in vivo imaging, immunophenotyping, RNA sequencing, and cell transfer protocols to characterize hepatic B cell subtypes from birth to adulthood. We found that newborn liver B cell population are transcriptionally and phenotypically distinct from those in adults, with significant alterations in genes related to immunoglobulin processing, release, and major histocompatibility complex class I and II functions. Photoconversion-based tracking revealed that liver-resident B cells actively migrate to distant lymphoid organs, including the spleen and bone marrow, where they integrate into the mature immune cell pool. Our findings establish the newborn liver as a crucial niche for B cell maturation and migration, highlighting its role in seeding secondary lymphoid organs and contributing to immune function throughout life. These insights provide new understanding of liver-derived B cells in the postnatal development of the immune system.