Abstract
Scientists have largely solved the century-old problem (Kindt and Capra 1984) of how the extraordinary range and specificity of the antibody response is generated. Multiple germline gene segments contribute to antibody diversity through combinatorial rearrangement, joining imprecision, and random insertion (N-diversity). Further diversity occurs through somatic hypermutation and/or somatic gene conversion of V(D)J genes, and by the pairing of immunoglobulin heavy and light chains. The comparative study of vertebrate immune systems shows that the number of germline V genes used in V(D)J gene rearrangement, as well as the mechanisms used in somatic diversification of V(D)J genes, varies among vertebrates. The rabbit has played an important role both in resolving the century-old problem of antibody diversity and in broadening the view of antibody diversification gained through mouse and human studies. In this chapter, we describe our current understanding of antibody diversification in the rabbit in the context of the historical contributions that rabbit studies have made to this field.
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