title: Mechanism of spontaneous activation of B cells in patients with systemic lupus erythematosus. Analysis with anti-class II antibody.
abstract: The mechanism of spontaneous activation of B cells in patients with systemic lupus erythematosus (SLE) was analyzed by using anti-class II monoclonal antibodies in vitro. B cells from SLE patients showed enhanced proliferation and Ig production by in vitro culture without any stimulation. The number of Ig-producing cells increased during a 5-day culture period, but the addition of anti-class II antibodies such as anti-HLA-DR, DQ, or DP monoclonal antibodies inhibited these B cell responses in a dose-dependent manner. Anti-class I and anti-B1 antibody gave no effect. The inhibitory effect of anti-class II antibodies on B cell responses became more remarkable when B cells were cultured on a longer period. By a Percoll gradient density centrifugation, Ig-producing cells were enriched in the lower density fraction, but became depleted in the higher density fraction. However, B cells of the higher density fraction developed into Ig-producing cells after 5 days of culture and anti-class II antibodies inhibited this development. When mitomycin C- and cycloheximide-treated B cells were added to the in vitro culture of B cells as a stimulator, B cell responses were enhanced in a dose-dependent manner. T cells treated with mitomycin C and cycloheximide had no enhancing effect on B cell responses. Furthermore, the enhancing effect of the stimulator B cells was inhibited by the pretreatment of stimulator B cells with anti-class II antibodies. These results suggest that in patients with SLE the abnormality exists in B precursor cells which are easily activated by interacting with other B cells to differentiate into Ig-producing cells and anti-class II antibodies inhibit the B cell activation by interfering with this cellular interaction.
authors.affiliation: First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: F
authors.initials: F
authors.lastname: Shirakawa
authors.forename: T
authors.initials: T
authors.lastname: Ota
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Eto
authors.forename: U
authors.initials: U
authors.lastname: Yamashita
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology*; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D006681:HLA-D Antigens / Q000276:immunology*; D006462:Hemolytic Plaque Technique; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation
chemical_list: D000911:Antibodies, Monoclonal; D006681:HLA-D Antigens; D007166:Immunosuppressive Agents