Although at first glance mechanisms used to create the variable domains of immunoglobulin appear to be designed to generate diversity at random, closer inspection reveals striking evolutionary constraints on the sequence and structure of these antigen receptors, suggesting that natural selection is operating to create a repertoire that anticipates or is biased towards recognition of specific antigenic properties. This Research Topics issue will be devoted to an examination of the evolution of antigen receptor sequence at the germline level, a detailed examination of the constraints observed in the structure of the variable domains, an evaluation of the development of the repertoire in primary and secondary lymphoid organs in mouse, rabbit and human, a discussion of how an examination of the repertoire can yield clues to the development of lymphoproliferative disorders, and a discussion of how study of the normal development and evolution of the repertoire informs the construction or selection of in vitro antibodies for applied purposes.
Although at first glance mechanisms used to create the variable domains of immunoglobulin appear to be designed to generate diversity at random, closer inspection reveals striking evolutionary constraints on the sequence and structure of these antigen receptors, suggesting that natural selection is operating to create a repertoire that anticipates or is biased towards recognition of specific antigenic properties. This Research Topics issue will be devoted to an examination of the evolution of antigen receptor sequence at the germline level, a detailed examination of the constraints observed in the structure of the variable domains, an evaluation of the development of the repertoire in primary and secondary lymphoid organs in mouse, rabbit and human, a discussion of how an examination of the repertoire can yield clues to the development of lymphoproliferative disorders, and a discussion of how study of the normal development and evolution of the repertoire informs the construction or selection of in vitro antibodies for applied purposes.