title: The HIV-1 envelope protein gp120 is captured and displayed for B cell recognition by SIGN-R1(+) lymph node macrophages.
abstract: The HIV-1 envelope protein gp120 is both the target of neutralizing antibodies and a major focus of vaccine efforts; however how it is delivered to B cells to elicit an antibody response is unknown. Here, we show that following local gp120 injection lymph node (LN) SIGN-R1(+) sinus macrophages located in interfollicular pockets and underlying SIGN-R1(+) macrophages form a cellular network that rapidly captures gp120 from the afferent lymph. In contrast, two other antigens, phycoerythrin and hen egg lysozyme, were not captured by these cells. Intravital imaging of mouse LNs revealed persistent, but transient interactions between gp120 bearing interfollicular network cells and both trafficking and LN follicle resident gp120 specific B cells. The gp120 specific, but not the control B cells repetitively extracted gp120 from the network cells. Our findings reveal a specialized LN antigen delivery system poised to deliver gp120 and likely other pathogen derived glycoproteins to B cells.
authors.affiliation: B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States.
authors.forename: Chung
authors.initials: C
authors.lastname: Park
authors.affiliation: Immunopathogenesis Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States.
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.affiliation: Immunopathogenesis Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.affiliation: B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000032:analysis*; D008198:Lymph Nodes / Q000276:immunology*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology; D010799:Phycoerythrin / Q000008:administration & dosage / Q000276:immunology; D011956:Receptors, Cell Surface / Q000032:analysis*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D004527:Egg Proteins; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D009113:Muramidase; D010799:Phycoerythrin; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: B lymphocyte; HIV-1; gp120; immunology; lymph node; mouse; vaccine