The assembled pre-BCR serves essential functions in the maturation of B cells:

• Signals from the pre-BCR complex promote the survival and proliferation of B lineage cells that have made a productive rearrangement at the Ig H chain locus. This is the first checkpoint in B cell development, and it selects and expands the pre-B cells that express a functional μ heavy chain (which is an essential component of the pre-BCR and BCR). Pre-B cells that make out-of-frame (nonproductive) rearrangements at the heavy-chain locus fail to make the μ protein, cannot express a pre-BCR or receive pre-BCR signals, and die by programmed cell death (apoptosis). The pre-BCR signaling pathway includes a downstream tyrosine kinase called Btk, which is encoded on the X chromosome. Mutations in Btk in boys results in the failure of pre-B cells to survive and the subsequent absence of B cells. This disease is called X-linked agammaglobulinemia.

• The pre-BCR complex signals to shut off recombination of Ig heavy-chain genes on the second chromo some, so each B cell can express an Ig heavy chain from only one of the two inherited parental alleles.

This process is called allelic exclusion, and it helps ensure that each cell can only express a receptor of a single specificity.

 • Signals from the pre-BCR complex shut off expression of the surrogate light-chain genes and open up the Ig κ light-chain locus making it available for recombination. The cells transiently stop dividing, and can express the μ protein only in the cytoplasm (and not on the cell surface) because they have no surrogate light-chain proteins or regular light-chain proteins. At this stage, these cells are called small pre-B cells.

• In small pre-B cells, V to J rearrangement of the κ light chain gene is initiated, leading to production of the κ protein and the assembly of cell surface IgM. The cells at this next stage of differentiation are called immature B cells. The λ light chain is produced only if the rearranged κ chain locus fails to express a functional protein or if the κ chain generates a potentially harmful self-reactive receptor and has to be eliminated, by a process called receptor editing, described later. In immature B cells, the BCR complex delivers signals that promote survival, thus preserving cells that express complete antigen receptors; this is the second checkpoint during B cell maturation. Signals from the antigen receptor also shut off production of the recombinase enzyme and further recombination at light-chain loci. As a result, each B cell produces either one κ or one λ light chain from one of the inherited parental alleles. The presence of two sets of light-chain genes in the genome simply increases the chance of completing successful gene recombination and receptor expression.