V(D)J Recombination: Of Mice and Sharks

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Abstract

The adaptive immune system of jawed vertebrates is based on a vast, anticipatory repertoire of specific antigen receptors, immunoglobulins (Ig) in B-lymphocytes and T-cell receptors (TCR) in T-lymphocytes. The Ig and TCR diversity is generated by a process called V(D)J recombination, which is initiated by the RAG recombinase. Although RAG activity is very well conserved, the regulated accessibility of the antigen receptor genes to RAG has evolved with the species’ organizational structure, which differs most significantly between fishes and tetrapods. V(D)J recombination was primarily characterized in developing lymphocytes of mice and human beings and is often described as an ordered, two-stage program. Studies in rabbit, chicken and shark show that this process does not have to be ordered, nor does it need to take place in two stages to generate a diverse repertoire and enable the expression of a single species of antigen receptor per cell, a restriction called allelic exclusion.