Nature of the scid Defect: A Defective VDJ Recombinase System

Lymphocyte antigen receptors include immunoglobulins (Ig) which consist of heavy (Igh) and light (Igl) chains, and T cell receptors (Tcr) which are composed of either α- and β-chains or of γ- and δ-chains. Early in lymphocyte development separate germline DNA segments, i.e., V, D and J or V and J, are assembled in recombinatorial fashion to form the genes that encode the variable, antigen-binding region of both Ig and Tcr proteins. (For reviews on this subject see: Tonegawa 1983; Kronenberg et al. 1986; Blackwell and Alt 1988; Davis 1988). It is thought that rearrangement of antigen-receptor genes proceeds in an ordered fashion although exceptions have been found. In general, D-to-J recombination occurs first followed by joining of a V gene segment to DJ. In B cell development, rearrangement of Iqh genes preceeds that of Iql genes. Likewise, in developing T cells the Tcrδ genes are rearranged as early as or earlier than Tcrγ and Tcrβ genes and followed by Tcrα gene rearrangement.