FIGURE 23-18 Structure of the pre-B-cell receptor and its role in B-cell development. Successful rearrangement of V, D, and J heavy-chain gene segments allows synthesis of membrane-bound µ heavy chains in the endoplasmic reticulum (ER) of a pre-B cell. At this stage, no light-chain gene rearrangement has occurred. Newly made µ chains assemble with surrogate light chains, composed of λ5 and VpreB, and Igα/Igβ to yield the pre-B-cell receptor, pre-BCR (step 1). This receptor drives proliferation of those B cells that carry it. It also suppresses rearrangement of the heavy-chain locus on the other chromosome and so mediates allelic exclusion. In the course of proliferation, the synthesis of λ5 and VpreB is shut off (step 2), resulting in “dilution” of the available surrogate light chains and reduced expression of the pre-BCR. As a result, rearrangement of the light-chain loci can proceed (step 3). If this rearrangement is productive, the B cell can synthesize light chains and complete assembly of the B-cell receptor (BCR), which consists of a membrane-bound IgM and associated Igα and Igβ. The B cell is now responsive to antigen-specific stimulation.