**1. Introduction**

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Development of B-lymphoid cells is a highly ordered multi-step process that, in adult mammals, starts in bone marrow in a pool of self-renewing multipotential hematopoietic stem cells, which gradually commit to the lymphoid lineage and advance through high regulated differentiation pathways until formation of mature functional cells. Over the last few years, exceptional advances have been recorded in identifying primitive progenitors that lay the foundations of the lymphoid program while losing myeloid potential, along with patterns of transcriptional activity controlling lineage fate decisions and environmental cues that influence the differentiation pathway during normal hematopoiesis. Multicolor flow cytometry, controlled cell cultures, genetic marking systems, microarray technologies and xenotransplantation approaches are being extensively used to address fundamental questions on this regard. Of special interest is the stem cell research with relevance to hierarchy and early events in malignant lymphopoiesis, and to new insights into perspectives that may allow progress in means to protect and sustain the immune system during chemotherapy, inflammation, infection, and following hematopoietic transplantation. In this book chapter, we focus on the hierarchical structure of the early lymphoid system, the current knowledge about intrinsic and microenvironmental factors regulating the differentiation of lymphoid progenitors, and the emerging research to understand malignant lymphoid development.
