The number and generative capacity of human B lymphocyte progenitors, measured in vitro and in vivo, is higher in umbilical cord blood than in adult or pediatric bone marrow Summary:The lack of human B lymphocyte development in beige/nude/XID (bnx) mice is in sharp contrast to the robust development observed in another immune deficient strain, the NOD/SCID mouse. The ability to generate human B lymphocytes in the NOD/SCID, but not bnx mouse has been hypothesized to be caused by differences in the microenvironments or systemic cytokine concentrations. In the current studies we report that the differences in development can be primarily attributed to the source of the progenitors transplanted into the mice. The prior studies in bnx mice used cultured pediatric or adult bone marrow (BM) as the source of the CD34 + cells, whereas the NOD/SCID studies have predominantly used fresh or cultured umbilical cord blood (UCB). We have analyzed BM and UCB for the number of human CD34 + /CD38 − cells capable of in vitro B lymphocyte development, and have found a lower frequency of B lymphocyte generation in BM. The individual B lymphocyte clones that developed from bone marrow produced 100-fold fewer cells than the UCB-derived clones. In agreement with the in vitro studies, human B lymphocytes developed in bnx mice from both CD34+ and CD34 + /CD38 − cells isolated from human umbilical cord blood, but not from equivalent numbers of CD34 + and CD34 + /CD38 − progenitors from bone marrow. Therefore, the lower generative capacity, and frequency of B lymphocyte precursors in human marrow may be responsible for the previous results that showed a lack of B lymphocyte development in bnx mice. Keywords: B lymphopoiesis; hematopoietic stem cells; CD34 ϩ progenitors; umbilical cord blood; bone marrowImmune deficient mouse xenograft systems are used to study the development of multilineage progeny from transplanted human hematopoietic stem and progenitor cells. The most successful murine strains used to date are the beige/nude/XID (bnx) and the NOD/LtSz-scid/scid (NOD/ scid). There are several differences in the two xenograft systems, including the mutations responsible for the murine immunodeficiencies, the duration of the engraftment assays that can be done, and the human hematopoietic lineages that develop. 1-13 The current report focuses on differences in development of human B lymphocytes from transplanted human hematopoietic stem and progenitor cells obtained from bone marrow vs umbilical cord blood, in the bnx/hu xenograft system. Reconstitution of the B lymphoid compartment after bone marrow transplantation can lag behind recovery of other hematopoietic lineages.14-16 Our studies indicate that human hematopoietic progenitors capable of reconstituting the B lymphocyte compartment in a xenogeneic transplant model (human to mouse) are scarce in human bone marrow, but comprise a higher percentage of human umbilical cord blood progenitors.We established a successful xenograft system using beige/nude/xid (bnx) mice as recipients of hu...