title: HIV-derived lentiviral particles promote T-cell independent activation and differentiation of naïve cognate conventional B2-cells in vitro.
abstract: In animal models, lentiviral particles (LP) were shown to be promising HIV vaccine candidates. Since little is known about the direct impact of LP on antigen-specific B cells, we incorporated Hen Egg Lysozyme (HEL) into LP (HEL-LP) derived from HIV to study their effect on HEL-specific, B cell receptor-transgenic B-cells (HEL(+)B-cells) in vitro. We observed preferential binding of HEL-LP to HEL(+)B-cells and their efficient internalization. HEL-LP were able to effectively cross-link B-cell receptors as indicated by the loss of surface CD62L. In the absence of CD4(+) T-cells, other activation events induced by LP in cognate naïve B-cells included increased expression of activation and co-stimulatory molecules as well as an enhanced proliferative response. Additionally, the B-cell phenotype shifted toward a germinal center pattern with further differentiation into memory and IgG3- and IgA-producing cells. The observed CD4(+) T-cell independent activation and differentiation may be due to LP-induced expression of CD40L by a subset of cognate B-cells. Thus, even in the absence of CD4(+) T-cells LP provide strong direct activation signals to cognate naïve B-cells, which may contribute to the strong humoral immune responses observed after LP immunization.
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gardt
authors.forename: Bastian
authors.initials: B
authors.lastname: Grewe
authors.forename: Bettina G
authors.initials: BG
authors.lastname: Tippler
authors.forename: Klaus
authors.initials: K
authors.lastname: Überla
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Temchura
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D057809:HEK293 Cells; D006678:HIV / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D014771:Virion / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D019041:L-Selectin; D023201:CD40 Ligand; C421864:hen egg lysozyme; D009113:Muramidase
keywords: B-cells; Lentiviral VLP; T-independent activation