Maternal T and B cell engraftment in two cases of X-linked severe combined immunodeficiency with IgG1 gammopathy

X-linked severe combined immunodeficiency (X-SCID), caused by defects in the common gamma chain, is typically characterized by T and NK cell defects with the presence of B cells. T cell dysfunction and impaired class-switch recombination of B cells mean that patients typically have defects in class-switched immunoglobulins (IgG, IgA, and IgE) with detectable IgM. Here, we describe two patients with X-SCID with IgG1 gammopathy, in whom we identified maternal T and B cell engraftment. Exclusively, maternal B cells were found among the IgD−CD27+ class-switched memory B cells, whereas the patients' B cells remained naïve. In vitro stimulation with CD40L+IL-21 revealed that peripheral blood cells from both patients produced only IgG1. Class-switched maternal B cells had restricted receptor repertoires with various constant regions and few somatic hypermutations. In conclusion, engrafted maternal B cells underwent class-switch recombination and produced immunoglobulin, causing hypergammaglobulinemia in patients with X-SCID. •Two cases of atypical X-SCID with IgG1 gammopathy had maternal T and B cell engraftment.•Only maternal B cells differentiated to class-switched memory B cells and produced IgG1.•Pre-class switched B cells engrafted then underwent class switch recombination in SCID patients.•This is the first report to identify maternal B cell engraftment in B+SCID.