Intrinsic defects of B cell function in X-linked severe combined immunodeficiency

The cytokine receptor common gamma chain mutation in X-linked SCID results in a failure of T and NK cell development and an as yet undefined defect of B cells. Using immunoglobulin isotype-specific reverse transcription-PCR w e show that although hematopoietic stem cell transplantation restores a div erse repertoire of class-switched B cell clones, on further analysis these are almost all of donor origin. This suggests that host B cells, which pred ominate after unconditioned transplantation, are still defective even in th e presence of normal T cells. These studies imply that effective humoral re constitution can only be achieved by the engraftment of normal donor B cell s.