PLoS Medicine (Jul 2009)

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

  • Marc C Levesque,
  • M Anthony Moody,
  • Kwan-Ki Hwang,
  • Dawn J Marshall,
  • John F Whitesides,
  • Joshua D Amos,
  • Thaddeus C Gurley,
  • Sallie Allgood,
  • Benjamin B Haynes,
  • Nathan A Vandergrift,
  • Steven Plonk,
  • Daniel C Parker,
  • Myron S Cohen,
  • Georgia D Tomaras,
  • Paul A Goepfert,
  • George M Shaw,
  • Jörn E Schmitz,
  • Joseph J Eron,
  • Nicholas J Shaheen,
  • Charles B Hicks,
  • Hua-Xin Liao,
  • Martin Markowitz,
  • Garnett Kelsoe,
  • David M Margolis,
  • Barton F Haynes

DOI
https://doi.org/10.1371/journal.pmed.1000107
Journal volume & issue
Vol. 6, no. 7
p. e1000107

Abstract

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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.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.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.