The role of the preBCR, the interleukin-7 receptor, and homotypic interactions during B-cell development.
Considerable progress has been made in defining intermediate stages in the process leading from stem cells to mature B cells. Cell-bound and secreted molecules direct the progression through these stages and regulate the selection of clones from which the immune repertoire emerges. In fact, a myriad of signals derived from B-cell progenitors themselves and the microenvironment in which they develop direct the differentiation process. These signals are provided by B-cell antigen receptors (BCR) and their surrogates, and by adhesion and cytokine receptors. The co-operation of these receptors to control survival, expansion, and differentiation of early B-cell progenitors is the topic of this review. Specifically, we will summarize recent findings from our laboratory demonstrating that preBCR expression lowers the threshold for interleukin (IL)-7 responsiveness. How signals initiated by these receptors may intersect at this critical point of B-cell selection will be discussed. At the stage following IL-7 responsiveness we have shown that interactions between B-cell progenitors themselves promote their differentiation to immunoglobulin-secreting B cells. We propose that one function of stromal cells, known to be central to B lymphopoiesis, is to promote critical preB-preB homotypic interactions and ensuing signals.
Department of Immunology, University of Toronto, Ontario Cancer Institute, University Health Network, Canada. stoddart@oci.utoronto.ca
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Stoddart
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Fleming
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Paige
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D015851:Interleukin-7 / Q000502:physiology; D008213:Lymphocyte Activation; D008954:Models, Biological; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000502:physiology*
D015851:Interleukin-7; D011947:Receptors, Antigen, B-Cell; D020395:Receptors, Interleukin-7