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 sele ction of clones from which the immune repertoire emerges. In fact, a myriad of signals derived from B-cell progenitors themselves and the microenviron ment in which they develop direct the differentiation process. These signal s 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 progenitor s is the topic of this review. Specifically, we will summarize recent findi ngs from our laboratory demonstrating that preBCR expression lowers the thr eshold for interleukin (IL)-7 responsiveness. How signals initiated by thes e receptors may intersect at this critical point of B-cell selection will b e discussed. At the stage following IL-7 responsiveness we have shown that interactions between B-cell progenitors themselves promote their differenti ation to immunoglobulin-secreting B cells. We propose that one function of stromal cells, known to be central to B lymphopoiesis, is to promote critic al preB-preB homotypic interactions and ensuing signals.