The ability to generate a diverse immune response depends on the somatic assembly of genes that encode the antigen-binding portions of immunoglobulin molecules. In this article, we discuss the mechanism and control of these genomic rearrangement events and how aspects of this process are involved in generating the primary antibody repertoire.

Immunoglobulin (Ig) variable (V) region genes are assembled in precursor B (pre-B) lymphocytes from multiple germline segments. The heavy-chain V-region gene is composed of variable (VH), diversity (D) and joining (JH) segments; kappa (K) and lambda (lambda) light-chain V-region genes have analogous VL and JL segments. Assembly of Ig V-gene segments, as well as those of the highly related T-cell receptor, is regulated at several levels and shows both stage and tissue specificity; for example Ig heavy-chain V-gene assembly precedes that of Ig light chains during B-cell differentiation. Joining of all classes of V-gene segments involves conserved recognition sequences that are probably targets for a common recombinase. Evidence has been presented suggesting that rearrangement of specific classes of segments is regulated by modulation of their accessibility to the recombinase. To elucidate mechanisms which control V-region gene assembly, we have investigated the effect of flanking gene expression on the frequency at which introduced V-gene segments are assembled in pre-B cell lines. Our findings suggest that transcription may play a direct role in the regulation of immunoglobulin V-gene assembly.

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