ABSTRACT
Following enunciation of the clonal selection theory of antibody formation by Burnet in 1957, experimental evidence confirms the validity of this selective theory as opposed to the instructive theory of antibody formation that prevailed during the first half of the 20th century. As immunogeneticists attempted to explain the great diversity of antibodies encoded by finite quantities of DNA, Tonegawa offered a plausible explanation for the generation of antibody diversity in his studies of immunoglobulin gene C, V, J, and D regions and their rearrangement. It is necessary for those segments that encode genes and determine immunoglobulin H and L chains to undergo rearrangement prior to gene transcription and translation. Newly synthesized immunoglobulin molecules have different properties based on their immunoglobulin class or isotype. Nevertheless, antigen-binding specificities reside in the Fab regions of antibody molecules, which governs their interactions with antigens in vitro and in vivo. By contrast, complement binding and activation capabilities, binding to cell surface, and transport through cells reside in the Fc region of the molecule. The fate of immunoglobulin molecules also differs according to the immunoglobulin class, each with its own characteristic half-life. Only IgG is protected from catabolism by binding to a specific receptor. Some antibodies are protective, others cross the placenta from mother to fetus, whereas others participate in hypersensitivity reactions that lead to adverse effects in target tissues. Antibodies are a diverse and unique category of proteins whose antigen-binding diversity is expressed in the 1020 antibody molecules synthesized from the 1012 B lymphocytes found in the human body.
