V(D)J recombination and somatic hypermutation (SHM) are the primary mechanisms for diversification of the human antibody repertoire. These mechanisms allow for rapid humoral immune responses to a wide range of pathogenic challenges. V(D)J recombination efficiently generate a virtually limitless diversity through random recombination of variable (V), diversity (D), and joining (J) genes with div...

The specificity of humoral immune responses relies on the huge DIVERSITY of antigen combining sites present in antibodies, diversity which is generated in an antigenindependent fashion. The process by which antigen (during an immune response) stimulates the clonal expansion and differentiation of antibody-forming cells of predetermined specificity is known as CLONAL SELECTION. The basic princip...

University of Chicago switch-specific endonuclease then cleaves the doubleChicago, Illinois 60637 strand DNA at random sites within or near Sm and the downstream S region involved in the particular switch. As the switch region repeats are varied, the endonucleAntibody molecules are encoded by immunoglobulin (Ig) ase(s) would not recognize a particular sequence but genes and are produced exclusi...

The initial antibody repertoire is determined by multiple heavy and light chain variable region (V. and VL) ~ gene segments and multiple joining gene segments (J~, Jx, JH, and D.). These gene segments can join in various combinations (1-8) and complete V gene products can associate in different combinations. As a result of combinational joining and association, the size of the preimmune reperto...

A single antibody was shown to adopt different binding-site conformations and thereby bind unrelated antigens. Analysis by both x-ray crystallography and pre-steady-state kinetics revealed an equilibrium between different preexisting isomers, one of which possessed a promiscuous, low-affinity binding site for aromatic ligands, including the immunizing hapten. A subsequent induced-fit isomerizat...