Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection

PLoS Med. 2009 Jul 7;6(7):e1000107. doi: 10.1371/journal.pmed.1000107. Epub 2009 Jul 7.


Background: The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreover, levels of HIV-1-specific antibodies decline on antiretroviral treatment. The mechanisms of this delay in the appearance of anti-HIV-1 antibodies and of their subsequent rapid decline are not known. While the effect of HIV-1 on depletion of gut CD4(+) T cells in acute HIV-1 infection is well described, we studied blood and tissue B cells soon after infection to determine the effect of early HIV-1 on these cells.

Methods and findings: In human participants, we analyzed B cells in blood as early as 17 days after HIV-1 infection, and in terminal ileum inductive and effector microenvironments beginning at 47 days after infection. We found that HIV-1 infection rapidly induced polyclonal activation and terminal differentiation of B cells in blood and in gut-associated lymphoid tissue (GALT) B cells. The specificities of antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI) included not only HIV-1-specific antibodies, but also influenza-specific and autoreactive antibodies, indicating very early onset of HIV-1-induced polyclonal B cell activation. Follicular damage or germinal center loss in terminal ileum Peyer's patches was seen with 88% of follicles exhibiting B or T cell apoptosis and follicular lysis.

Conclusions: Early induction of polyclonal B cell differentiation, coupled with follicular damage and germinal center loss soon after HIV-1 infection, may explain both the high rate of decline in HIV-1-induced antibody responses and the delay in plasma antibody responses to HIV-1. Please see later in the article for Editors' Summary.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Apoptosis / immunology
  • Autoimmunity
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / immunology
  • Female
  • Germinal Center / pathology*
  • Germinal Center / virology
  • HIV Antibodies / blood*
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Ileum / immunology*
  • Ileum / pathology
  • Ileum / virology
  • Influenza, Human / immunology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Peyer's Patches / pathology
  • Peyer's Patches / virology
  • Time Factors
  • Young Adult


  • Antibodies, Viral
  • HIV Antibodies