Only a subpopulation of relatively large pre-B cells express pre-B cell receptors (preBCR) that can be seen with very sensitive immunofluorescence methods. Inefficient assembly of the multicomponent preBCR coupled with their ligand-induced endocytosis may account for the remarkably low in vivo levels of preBCR expression. Signaling initiated via the preBCR promotes cellular proliferation and RAG-1 and RAG-2 downregulation to interrupt the immunoglobulin V(D)J gene rearrangement process. Silencing of the surrogate light chain genes, VpreB and λ5, then terminates preBCR expression to permit cell cycle exit, recombinase gene upregulation, and VJL rearrangement by small pre-B cells destined to become B cells. © 2002 Elsevier Science Ltd. All rights reserved.