A family study of the x-linked lymphoproliferative syndrome: evidence for a B cell defect contributing to the immunodeficiency

The X-linked lymphoproliferative syndrome (XLPS) is an immunodeficiency characterized by severe primary infection with the Epstein Barr (EB) virus, which is often fatal. This has been attributed to failure to generate T lymphocytes which are specifically cytotoxic for EB virus-infected B lymphocytes, and which develop in all normal individuals following primary infection. We have studied a kindred which carried the defective gene for XLPS and have confirmed that the pattern of serum antibody responses to EB viral antigens can be used to detect affected males and female carriers. Furthermore, an EB virus genome-carrying B cell line which grew spontaneously from a culture of bone marrow cells from a male child with XLPS at the time of primary infection showed a decreased sensitivity to MHC-restricted, EB virus-specific killing by a T cell clone when compared to its in vitro EB virus-transformed counterpart. From these results we suggest that a subset of EB virus-infected B lymphocytes which were resistant to EB virus-specific killing existed in this child, and may have contributed to the overwhelming EB virus infection and its fatal outcom