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. DH→ JH rearrangements are found in almost all cells of fraction B. VH→ DHJH rearrangement occurs in fractions C and C (2). Cells in fractions B to C are also called pre-B I cells. As soon as H chain proteins appear in the cytoplasm and can be assembled into a functional precursor B cell receptor (pre-BCR), pre-B I cells develop into large pre-B II cells that are c-kit and CD43 negative (3). Successful rearrangement of the H chain and a correctly assembled pre-BCR associated with a functional signaling machinery allow pre-B II cells to proliferate. How is this proliferation controlled, what stimulates it, and what terminates it? When proliferation stops, pre-B II cells become smaller (so-called small pre-B II) and rearrangement starts again, this time in the L chain locus. Immature B cells subsequently express a complete IgM molecule on their surface. B cells leave the bone marrow at the transitional B cell stage and complete their final development into mature B cells in the periphery (4). Analysis of mice with mutations of genes involved in the rearrangement process and in BCR signaling has shown that the pre-BCR (2) and the BCR (4) regulate the progression of cells of the B lineage along their differentiation pathway at earlier and later stages of development, respectively. However, the microenvironment in the bone marrow also plays a role of fundamental importance. When HSCs are injected intravenously, long-term B cell poiesis is established only in the bone marrow, suggesting that only this microenvironment supports the growth and differentiation of cells of the B lineage in the adult. The liver functions as the site of hematopoiesis only transiently, during the fetal life. Although stromal cells are the key elements of the microenvironment of the bone marrow, very little is known about their biological diversity and functional characteristics (5). Stromal cells form a network in the intersinusoidal spaces of the bone cavity that extends from the endostium to the endothelial cell basement membrane of the sinusoids. Hematopoietic cells differentiate and proliferate in the interstices of this network in close contact with long cytoplasmic processes of stromal cells (6, 7). One major function of stromal cells is the production of IL-7. IL-7 was originally cloned from a stromal cell line as a factor supporting the growth of pre-B cells in vitro. Because pre-B cells do not grow on stromal cells that fail to produce IL-7, this cytokine is an indispensable requirement for B cell development (8). The receptor for IL-7 (IL-7R) on lymphocytes is a heterodimer composed of an and ac chain. The chain is shared by the IL-7R and by the receptor for the recently identified cytokine thymic stromal lymphopoietin (TSLP [9]). The common c chain is employed for signaling purposes by receptors for IL-2, IL-4, IL-9, and IL-15 in addition to IL-7 (10). The generation of mice deficient for individual elements of the IL-7/IL-7R system has shed light on the in vivo function of this cytokine. Mice that lack …