On the Possible Role of Natural Reverse Genetics in the V Gene Loci
The immune system of higher vertebrates has evolved to mount destructive responses which eliminate infectious agents. These responses depend upon a large population of mobile cells (lymphocytes) each of which expresses multiple copies of a particular receptor for antigen. The receptors are encoded by large multigene families in germline DNA, but before expression of receptor proteins in lymphocytes (each with a heterodimeric binding site for antigen) the germline genes undergo a unique rearrangement process in which two or three separate genetic elements are brought together to form the final coding sequence for the variable (V) portion of each of the two receptor protein chains (Tonegawa 1983). Another separate element encodes the constant (C) region of the receptor protein which, in the case of the heavy chains of immunoglobulins and both chains of T cell receptors, spans the cell membrane and is an integral part of the signalling mechanism which activates lymphocyte responses to antigen. In the case of B lymphocytes, soluble immunoglobulins are secreted which have the same antigen-binding specificity as the receptor on each individual cell and which mediate effector functions through the constant region of the secreted antibody molecule.
KeywordsGene Conversion Functional Versus Somatic Hypermutation Upstream Boundary Strand Bias
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