title: Reduced memory B-cell populations in boys with B-cell dysfunction after bone marrow transplantation for X-linked severe combined immunodeficiency.
abstract: X-linked severe combined immunodeficiency (XSCID) is a lethal disease resulting in death in infancy. In many instances, haploidentical bone marrow transplantation (BMT) offers reconstitution of T-cell immunity alone, with residual hypogammaglobulinaemia. The exact nature of B-cell dysfunction in these patients is unclear, although differentiation arrest of the B cells is a potential explanation. To ascertain the differentiation status of peripheral blood B lymphocytes from XSCID patients after BMT, the surface expression of CD19, CD10, CD34, CD5, serum immunoglogulin (sIg)M, sIgD, sIgG and CD27 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 were found to be diminished in the XSCID patients after BMT with persistent hypogammaglobulinaemia, compared with both post-BMT patients with B-cell function 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 CD19+IgM-only and CD19+IgG+CD27+ or CD19+IgM+CD27+ memory B-cell 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 hypogammaglobulinaemia in these patients after BMT.
authors: Sydney Children's Hospital, High St., Randwick, NSW 2031, Sydney, Australia.
authors: S S
authors: SS
authors: Ting
authors: S G
authors: SG
authors: Tangye
authors: J
authors: J
authors: Wood
authors: R A
authors: RA
authors: Ffrench
authors: J B
authors: JB
authors: Ziegler
mesh_terms: D000361:Agammaglobulinemia / Q000276:immunology; D018941:Antigens, CD19 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation; D018956:CD5 Antigens / Q000032:analysis; D016022:Case-Control Studies; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D007072:Immunoglobulin D / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007156:Immunologic Memory; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D015260:Neprilysin / Q000032:analysis; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000628:therapy*; D018709:Statistics, Nonparametric; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D014960:X Chromosome
chemical_list: D018941:Antigens, CD19; D018952:Antigens, CD34; D018956:CD5 Antigens; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015260:Neprilysin