The Development of B Cells in the Bone Marrow Is Controlled by the Balance between Cell-Autonomous Mechanisms and Signals from the Microenvironment

B cells are generated from hematopoietic stem cells (HSCs) in the liver during the fetal life, and in the bone marrow in the adult. The differentiation pathway from HSC to mature B cell can be divided into several stages, based on the phenotype and on functional properties that cells of the B lineage progressively acquire. Progenitor B (pro-B) cells can be identified by cell surface expression of B220, CD43, and c-kit. Differential expression of heat-stable antigen (HSA) and of the maturation marker BP-1 discriminates four fractions of pro-B cells (fractions A, B, C, and C′ 1). At this stage of development, DNA rearrangement begins in the Ig H chain locus. Most pro-B cells of fraction A carry Ig genes in germline configuration. D_H→J_H rearrangements are found in almost all cells of fraction B. V_H...