Reduced memory B-cell populations in boys with B-cell dysfunction after bone marrow transplantation for X-linked severe combined immunodeficiency

X-linked severe combined immunodeficiency (XSCID) is a lethal disease resul ting in death in infancy. In many instances, haploidentical bone marrow tra nsplantation (BMT) offers reconstitution of T-cell immunity alone, with res idual hypogammaglobulinaemia. The exact nature of B-cell dysfunction in the se patients is unclear, although differentiation arrest of the B cells is a potential explanation. To ascertain the differentiation status of peripher al blood B lymphocytes from XSCID patients after BMT, the surface expressio n of CD19, CD10, CD34, CD5, serum immunoglogulin (sIg)M, sIgD, sIgG and CD2 7 on these B cells was investigated using three-colour flow cytometry. CD27 is a marker of memory B cells. Populations of CD19(+) IgM(-)D(-) B cells, CD19(+)IgM-only, CD19(+)IgG(+)CD27(+) and CD19(+)IgM(+) CD27(+) B cells wer e found to be diminished in the XSCID patients after BMT with persistent hy pogammaglobulinaemia, compared with both post-BMT patients with B-cell func tion and age-matched normal controls. This indicated the lack of CD19(+)IgM (-)D(-) B cells, which represent Ig isotype-switched B cells, as well as CD 19(+)IgM-only and CD19(+)IgG(+)CD27(+) or CD19(+)IgM(+)CD27(+) memory B-cel l populations. Interaction between CD27 and its ligand CD70 has been shown to induce IgG and IgM production by CD27(+) B cells. Therefore, the lack of CD27/70 interaction is a probable explanation for the hypogammaglobulinaem ia in these patients after BMT.