Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. Contribution of antibody-producing B cells, of Epstein-Barr virus-infected B cells, and of immunoglobulin production induced by human T cell lymphotropic virus, type III/lymphadenopathy-associated virus.
Patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) have hyperimmunoglobulinemia and increased numbers of circulating immunoglobulin-secreting cells. In this paper, we studied the basis for this B cell hyperactivity. Limiting dilution studies of B cells from seven patients with ARC and four with AIDS revealed that some B cells spontaneously produced antibodies to human T cell lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV) (39:10(6) and 7:10(6) B cells, respectively), suggesting that chronic antigenic stimulation by HTLV-III/LAV was one contributing factor. The patients also had an increased number of spontaneously outgrowing B cells than did normals (6:10(6) vs. less than 2:10(6) B cells), suggesting that they had an increased number of Epstein-Barr virus (EBV)-infected B cells. However, fewer B cells from patients were immortalized by exogenously added EBV than were B cells from normals. In additional studies, HTLV-III/LAV induced immunoglobulin secretion (mean 2,860 ng/ml) by peripheral blood mononuclear cells from normals; this HTLV-III/LAV-induced immunoglobulin secretion required the presence of both B and T cells. Thus, antigenic stimulation by HTLV-III/LAV, increased numbers of EBV-infected B cells, and HTLV-III/LAV-induced T cell-dependent B cell activation all contribute to the B cell hyperactivity in patients with HTLV-III/LAV disease.
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002472:Cell Transformation, Viral; D017977:Deltaretrovirus / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis / Q000096:biosynthesis*; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation
D000914:Antibodies, Viral; D007136:Immunoglobulins