Antibody Diversity: A Contemporary Solution
As stressed from the beginning of this book, for over three decades immunologists have appreciated that over a million different antibody specificities are likely extant in each vertebrate organism. Gradually over the past twenty years, immunologists came to espouse one of two major theories to explain the origin of this potential diversity. Many adhered to the germline theory; that is, for every antibody variable region structure there was a corresponding gene in germline DNA. A consequence of this model is that the genome must contain thousands if not millions of genes encoding antibody variable regions. Other immunologists adhered to the somatic diversification theory that postulated that a few inherited genes undergo extensive somatic alteration to generate the thousands of genes that give rise to the myriad of antibodies. In addition to the two major theories were the maverick solutions that suggested that antibody diversity might be due to new and radically different mechanisms; for example, that two or more genes could interact to form an immunoglobulin variable region. Over the past five years, data have accumulated indicating that all of these theories are correct, at least in part. There are multiple germline genes but not as many as anticipated by the germline theory. There is, indeed, somatic mutation of V-region (and J and D region) gene segments but this operates on a greater number of germline genes than was anticipated by the somatic theory.
KeywordsLight Chain Heavy Chain Somatic Mutation Gene Segment Germline Gene
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