1. Immunology and Inflammation
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The HIV-1 envelope protein gp120 is captured and displayed for B cell recognition by SIGN-R1+ lymph node macrophages

  1. Chung Park
  2. James Arthos
  3. Claudia Cicala
  4. John H Kehrl  Is a corresponding author
  1. National Institutes of Allergy and Infectious Diseases, United States
Research Article
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Cite this article as: eLife 2015;4:e06467 doi: 10.7554/eLife.06467

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.

Article and author information

Author details

  1. Chung Park

    B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. James Arthos

    Immunopathogenesis Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Claudia Cicala

    Immunopathogenesis Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. John H Kehrl

    B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, Bethesda, United States
    For correspondence
    jkehrl@niaid.nih.gov
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (LIR-15) of the National Institute of Allergy and Infectious Diseases.

Reviewing Editor

  1. Michel Nussenzweig, Rockefeller University, United States

Publication history

  1. Received: January 13, 2015
  2. Accepted: August 8, 2015
  3. Accepted Manuscript published: August 10, 2015 (version 1)
  4. Accepted Manuscript updated: August 12, 2015 (version 2)
  5. Version of Record published: August 28, 2015 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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Further reading

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