The ability to mount a specific immune response is dependent on antigen-specific B and T cells. During development, each B cell creates a novel immunoglobulin heavy (IgH) chain and immunoglobulin light (IgL) chain gene from germline-encoded gene segments through the process of V (D) J recombination. Each T cell uses an identical recombination process to create a unique T cell receptor (TCR) composed of a heterodimer of either the a6 gene products or yS gene products. V (D) J recombination can create a set of antigen-receptor genes of greater complexity than the sum of the rest of the genes encoded within the mammalian genome. The regulation of V (D) J recombination and the developmental selection of antigen-restricted lymphocytes has been a focus of intense research in recent years. Immunologists have marveled at the intricacies of this elegant process and pondered how it arose in evolution. Current evidence suggests that the ability to mount an antigen-specific immune response arose over a relatively short period of time coincident with the development of the first jawed vertebrates. This has raised the question of how a mechanism as complex as V (D) J recombination arose over such a short evolutionary period. Recent advances in V (D) J recombination suggest a resolution to this issue and allow us to reexamine the role of antigen specificity in shaping the evolution of the immune system.

V (D) J Recombination The main feature that separates vertebrate from invertebrate immune systems is the ability to generate antigenspecific lymphoid cells. Antibodies and TCRs play a central role in the vertebrate immune system because of their ability to recognize specific molecular antigens and thus initiate an antigen-specific immune response. Diversity within immunoglobulin andTCRs in mammals resultsfrom a series of somatic rearrangement events, which occur during lymphoid differentiation, culminating in the production of a functional cell surface immunoglobulin molecule in B cells, or a TCR in T cells (for a recent review see Lewis, 1994). A unique immunoglobulin receptor is created in each B cell during development. A functional IgH chain gene is assembled from an assortment of V, D, and J gene segments, while a functional L chain gene is assembled from an assortment of V and J sequences. The joining events generate further diversity through variations in the precise joining points of the coding elements as well as de