title: Fusion of human B cell lines with HIV-1 envelope-expressing T cells is enhanced by antigen-specific Ig receptors. Possible mechanism for elimination of gp120-specific B cells in vivo.
abstract: The possible contribution of Ag-specific Ig receptors on B cells to syncytium formation with HIV-1 envelope (env)-expressing cells was examined. A unique model system was designed that used anti-TNP/TNP interactions between a panel of TNP-specific human B cell lines and TNP-haptenated HIV-1 env-expressing T cells. The prototype B cell line 1:13 (CD4dull) produced few syncytia with vaccinia gp120/41-infected CD4- T cell effectors. However, TNP-haptenation of the HIV-1 env-expressing cells resulted in a five- to 10-fold increase in syncytium formation. The "enhanced" syncytia were blocked by OKT4A mAb, soluble CD4, anti-TNP serum, and TNP-BSA, suggesting a role for both CD4 and Ig receptors. In contrast, the number of syncytia formed between CD4+ CEM T cells and TNP-haptenated effectors was reduced by 30 to 40%, compared with the unhaptenated effectors, suggesting that a fraction of the TNP haptens bound close to the CD4 binding regions on the gp120 envelope, which was confirmed by other experiments. The possibility that B cells specific for the CD4 binding site on HIV-1 gp120 may be involved in syncytium formation with HIV-1 env-expressing cells was tested by screening a panel of five hybrid B cell lines from HIV-1-seropositive individuals. One of these lines produced anti-gp120 antibodies, which bound near the CD4 binding site, and also formed syncytia with HIV-1 env-expressing cells. This study suggests that, in addition to CD4 receptors, certain B cell Ig receptors that bind to gp120 may induce conformational changes leading to cell fusion and their elimination.
authors.affiliation: Division of Virology, Food and Drug Administration, Bethesda, MD 20892.
authors.forename: H
authors.initials: H
authors.lastname: Golding
authors.forename: D S
authors.initials: DS
authors.lastname: Dimitrov
authors.forename: R
authors.initials: R
authors.lastname: Blackburn
authors.forename: J
authors.initials: J
authors.lastname: Manischewitz
authors.forename: R
authors.initials: R
authors.lastname: Blumenthal
authors.forename: B
authors.initials: B
authors.lastname: Golding
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D015704:CD4 Antigens / Q000502:physiology; D002459:Cell Fusion; D002460:Cell Line; D002461:Cell Line, Transformed; D000939:Epitopes; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004854:Herpesvirus 4, Human; D006801:Humans; D008212:Lymphocyte Depletion; D010641:Phenotype; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011961:Receptors, Fc / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D014301:Trinitrobenzenes