Characterization of the suppressor activity in lymphocytes from patients with common variable hypogammaglobulinemia: evidence for an associated primary B-cell defect.
The pathogenetic mechanisms responsible for the impaired immunoglobulin production in common variable hypogammaglobulinemia (CVH) are diverse with abnormalities in both B cells and immunoregulatory T cells. Production of IgG, IgM, and IgM-rheumatoid factor (IgM-RF) was measured in pokeweed mitogen (PWM) or Epstein-Barr virus (EBV)-stimulated cultures using various combinations of CVH, cord blood mononuclear cells (CBMC), and normal adult control B and T cells. The following results were obtained. First, the proportion of OKT3+ and OKT8+ cells were increased in CVH patients. Second, the T cells from four CVH patients and CBMC suppressed PWM-induced IgG, IgM, and IgM-RF production by normal B cells. Furthermore, major suppressor activity was found in the OKT8+ T-cell subpopulations in CBMC and three out of four CVH patients. There was no significant difference in relative suppression by OKT8+ cells from normal adults, CVH patients, or CBMC. However, in one CVH patient suppressor T cells were found in both OKT4+ as well as OKT8+ fractions. In the CVH patient with OKT4+ suppressor cells, X irradiation (1250 rads) abrogated suppressor activity and restored helper activity in the OKT4+ T-cell fraction. Irradiation of normal OKT4+ cells did not increase helper activity. When non-E-rosetting cells from normal subjects, CVH, and CBMC were stimulated with EBV it was observed that normal adult B cells could be induced to secrete IgG, IgM, and Ig-RF whereas CVH and CBMC could only produce IgM and IgM-RF but not IgG. The present study demonstrates for the first time that a radiosensitive OKT4+ suppressor cell is present in some CVH patients.
D000361:Agammaglobulinemia / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D008213:Lymphocyte Activation; D011043:Pokeweed Mitogens; D012217:Rheumatoid Factor / Q000235:genetics; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens; D012217:Rheumatoid Factor