MOLECULAR-BASIS OF SELECTIVE IGG2 DEFICIENCY - THE MUTATED MEMBRANE-BOUND FORM OF GAMMA-2 HEAVY-CHAIN CAUSED COMPLETE IGG2 DEFICIENCY IN 2 JAPANESE SIBLINGS

Patients with IgG2 deficiency have recurrent sinopulmonary infections caused by Pneumococcus and Hemophilus, Hereditary and selective IgG2 d eficiency was suspected in two Japanese siblings whose serum IgG2 leve ls were under detection limits, while other serum levels of immunoglob ulin subclasses were within normal ranges, Expression level of spontan eous germline C gamma 2 transcript was normal, but that of the spontan eous mature C gamma 2 transcript was greatly decreased in the patients ' PBMCs, suggesting the presence of a defect at or after the class swi tch to C gamma 2, We sequenced the C gamma 2 gene region, and in both patients a homozygous one-base insertion (1793insG) was present in exo n 4 of the C gamma 2 gene, just upstream from the alternative splice s ite for M exons, The mutant membrane-bound gamma 2 heavy chain loses t he transmembrane domain and the evolutionarily conserved cytoplasmic d omain, Considering several lines of evidence showing that intact expre ssion of the membrane-bound heavy chain is essential for a normal resp onse of B cells and production of secreted immunoglobulin in mice, we concluded that 1793insG is responsible for selective and complete IgG2 deficiency in these two siblings, This is the first documentation of a mutation in human selective IgG2 deficiency.