title: Evidence for a defect in "switch" T cells in patients with immunodeficiency and hyperimmunoglobulinemia M.
abstract: Immunodeficiency with hyperimmunoglobulinemia M is a syndrome characterized by normal to elevated serum levels of IgM and low levels or absence of IgG and IgA. The defect in this syndrome is thought to reside within the B lymphocyte, which may be unable to undergo a "switch" in immunoglobulin class from IgM to IgG or IgA. To address this question more directly, we cultured B cells from nine patients with this syndrome with pokeweed mitogen and either "switch" T cells or normal control T cells. In cultures with normal T cells, only IgM was secreted, whereas in cultures with switch T cells, IgG as well as IgM, or IgM, IgG, and IgA were secreted. Furthermore, analysis of the immunoglobulin heavy-chain genes in these B cells by means of genetic probes of constant and switch regions revealed normal gene patterns. These data suggest that B cells from patients with hyperimmunoglobulinemia M may not be abnormal, as previously proposed, and that, at least in some patients with this syndrome, a defect in switch T cells may be pathogenic.
authors.forename: L
authors.initials: L
authors.lastname: Mayer
authors.forename: S P
authors.initials: SP
authors.lastname: Kwan
authors.forename: C
authors.initials: C
authors.lastname: Thompson
authors.forename: H S
authors.initials: HS
authors.lastname: Ko
authors.forename: N
authors.initials: N
authors.lastname: Chiorazzi
authors.forename: T
authors.initials: T
authors.lastname: Waldmann
authors.forename: F
authors.initials: F
authors.lastname: Rosen
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D004406:Dysgammaglobulinemia / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology*; D017098:IgA Deficiency; D017099:IgG Deficiency; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D004247:DNA