Key Concepts of Section 23.3

• Functional antibody-encoding genes are generated by somatic rearrangement of multiple DNA segments at the heavy-chain and light-chain loci. These rearrangements involve V and J segments for immunoglobulin light chains and V, D, and J segments for immunoglobulin heavy chains (see Figure 23-15).

• Rearrangement of immunoglobulin gene segments is controlled by conserved recombination signal sequences (RSSs) composed of heptamers and nonamers separated by 12- or 23-bp spacers (see Figure 23-16). Only those segments that have spacers of different lengths can rearrange successfully: two segments to be joined must possess a 12- and a 23-bp spacer, not two of identical length.

• The molecular machinery that carries out the rearrangement process includes proteins made only in lymphocytes (recombinases RAG1 and RAG2), but other proteins that are used in other types of cells participate in nonhomologous end joining of DNA molecules.

• Antibody diversity is created by the random selection of Ig gene segments to be recombined and by the ability of the heavy and light chains produced from rearranged Ig genes to associate with many different light chains and heavy chains, respectively.

• Junctional imprecision generates additional antibody diversity at the joints of the gene segments brought together by somatic gene rearrangements.

• Further antibody diversity arises after B cells encounter antigen as a consequence of somatic hypermutation, which can lead to the selection and proliferation of B cells producing the highest-affinity antibodies, a process termed affinity maturation.

• During B-cell development, heavy-chain genes are rearranged first, leading to expression of the pre-B-cell receptor. Subsequent rearrangement of light-chain genes results in assembly of an IgM membrane-bound B-cell receptor (see Figure 23-18).

• Only one of the allelic copies of the heavy-chain locus and of the light-chain locus is rearranged (allelic exclusion), ensuring that a B cell expresses Ig with a single antigenic specificity.

• Polyadenylation at different poly(A) sites in an Ig primary transcript determines whether the membrane-bound or secreted form of an antibody is produced (see Figure 23-19).

• During an immune response, class switching allows B cells to adjust the class of antibody made, and thus the effector functions of the immunoglobulins produced, while retaining the antibody’s specificity for antigen (see Figure 23-20).