A. Stoddart et al., The role of the preBCR, the interleukin-7 receptor, and homotypic interactions during B-cell development, IMMUNOL REV, 175, 2000, pp. 47-58
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.