Mammalian B cell development originates primarily in the fetal liver, and continues in neonatal bone marrow (BM) and adult BM throughout life. An expansive body of published data has provided a detailed account of the patterns of gene expression that characterize discrete stages of murine and human B cell development (1, 2). Targeted disruption of genes encoding transcription factors, immunoglobulin heavy and/or light chains and a variety of kinases have revealed the contribution of these molecules to the traversal of distinct checkpoints in B cell development (3, 4). Cytokines (i.e., interleukins, chemokines, interferons, and colony-stimulating factors), the ECM, and stromal cell components of the BM microenvironment play a crucial role in regulating the survival, proliferation, differentiation, and death of B lineage cells (5). Immunologists are accustomed to thinking about the role of these well-studied molecules in B cell development, but what about the role of something so fundamental as an amino acid? An intriguing report by de Jonge and colleagues in this issue of the JCI (6) identifies the amino acid arginine as being unexpectedly important in a specific stage of murine B cell development.