The interaction of immunoglobulin heavy and light chains in the absence of the V(H) domain

Recent studies of the μ and kappa chains of the first patient (GLI) with μHCD indicated that the observed defect was the result of the failure of assembly of the intact kappa chain to the μ chain, which lacked the V(H) domain but had the C(H)1 Cys normally linked to the light chain. To explore the possibility that the V(H) region is necessary for the formation of the HL disulfide bond, in vitro studies were performed with GLI μ and kappa chains and with the C(H)1 domain and kappa chain derived from an IgG3 myeloma protein, KUP, which yields separate V(H), C(H)1, and kappa chains after papain digestion and reduction. The proteins were reduced and allowed to reoxidize, and the combination products were assessed by gel chromatography under dissociating conditions by SDS PAGE and by immunoprecipitation techniques. The results suggest that, although in vitro covalent and noncovalent combinations are possible between intact light chains and their autologous heavy chains even in the absence of the V(H) domain, the efficiency is less than that when the intact Fd region is used. Hence, it seems likely that lack of V(H) alone is not sufficient to explain the failure of assembly observed in μHCD.