To produce antibodies with only one type of antigen-binding site, a developing B cell must use only one L-chain gene-segment pool and one H-chain pool. Although the choice between maternal and paternal pools is thought to be random, the assembly of V-region coding sequences in a developing B cell proceeds in an orderly sequence, one segment at a time, usually beginning with the heavy-chain pool. In this pool, D segments first join to J_H segments on both parental chromosomes; then V_H to DJ_H joining occurs on one of these chromosomes (not shown). If this rearrangement produces a functional gene, the resulting production of complete μ chains (always the first heavy chains made) leads to their expression on the cell surface in association with surrogate light chains. The cell now shuts down all further rearrangements of V_H-region-encoding gene segments and initiatesV_L rearrangement. Although not shown, V_L rearrangement usually occurs first in a κ gene-segment pool, and only if that fails does it occur in the other κ pool or in the λ pools. If, at any point, “in-phase” V_L-to-J_L joining leads to the production of light chains, these combine with preexisting μ chains to form IgM antibody molecules, which insert into the plasma membrane. The IgM cell-surface receptors are thought to enable the newly formed B cell to receive extracellular signals that shut down all further V(D)J joining, by turning off the expression of the rag-1 and rag-2 genes. If a developing B cell makes a receptor that recognizes a self-antigen, it is stimulated to re-express the rag genes and undergo another round of V(D)J joining (called receptor editing), thereby changing the specificity of its receptor (not shown). If a cell fails to assemble both a functional V_H-region and a functional V_L-region coding sequence, it is unable to make antibody molecules and dies by apoptosis (not shown).