ABSTRACT

Introduction 182 Pluripotent hematopoietic stem cells 182 Self-renewal 184 Pluripotency 184 Environmental influences on hematopoietic 184

differentiation potencies Hematopoietic cell-autonomous influences on 185

differentiation potencies Exclusive B-versus T-lymphoid lineage decisions 185 Modes of commitment to the B lymphocyte lineage 187

of differentiation Reversible decisions of exclusive B cell differentiation – 187

the flexibility of pluripotent cells Embryonic development of B lymphocytes 188

B lymphocyte compartments of the immune system 188 of mice and humans

The role of pre-B cell receptors in repertoire selections 190 of developing B cells

Generation of immature, sIgM B cell repertoires 192 Negative and positive selection – and ignorance of 193

the repertoire of developing immature B cells Negative selection and ‘editing’ 194 Ignorance 194 Positive selection 195 Peripheral B cells without immunoglobulin 196 Key points 197 References 197

A single pluripotent hematopoietic stem cell (pHSC) is capable of generating all the erythocytes, megakaryocytes, and blood platelets; all the cells of the myeloid cell lineages, such as monocytes, macrophages, dendritic cells, granulocytes (i.e., neutrophils, basophils, eosinophils, and mast cells), and osteoclasts; all the natural killer (NK) cells; the T lymphocytes – and the B lymphocytes. This chapter describes the major known molecular steps and cellular stages, and the interactions with the endogenous environment of cooperating cells, as well as with the exogenous environment of antigens and polyclonal activators, that begins with the generation of a pluripotent hematopoietic stem cell and finally leads to the deposition and use of mature B cells in different compartments of the immune system.