title: Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.
abstract: 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.
  
  
  RESULTS
  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.
authors: Department of Medicine, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors: Marc C
authors: MC
authors: Levesque
authors: M Anthony
authors: MA
authors: Moody
authors: Kwan-Ki
authors: KK
authors: Hwang
authors: Dawn J
authors: DJ
authors: Marshall
authors: John F
authors: JF
authors: Whitesides
authors: Joshua D
authors: JD
authors: Amos
authors: Thaddeus C
authors: TC
authors: Gurley
authors: Sallie
authors: S
authors: Allgood
authors: Benjamin B
authors: BB
authors: Haynes
authors: Nathan A
authors: NA
authors: Vandergrift
authors: Steven
authors: S
authors: Plonk
authors: Daniel C
authors: DC
authors: Parker
authors: Myron S
authors: MS
authors: Cohen
authors: Georgia D
authors: GD
authors: Tomaras
authors: Paul A
authors: PA
authors: Goepfert
authors: George M
authors: GM
authors: Shaw
authors: Jörn E
authors: JE
authors: Schmitz
authors: Joseph J
authors: JJ
authors: Eron
authors: Nicholas J
authors: NJ
authors: Shaheen
authors: Charles B
authors: CB
authors: Hicks
authors: Hua-Xin
authors: HX
authors: Liao
authors: Martin
authors: M
authors: Markowitz
authors: Garnett
authors: G
authors: Kelsoe
authors: David M
authors: DM
authors: Margolis
authors: Barton F
authors: BF
authors: Haynes
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000473:pathology* / Q000821:virology; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007082:Ileum / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007251:Influenza, Human / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010581:Peyer's Patches / Q000473:pathology / Q000821:virology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015483:HIV Antibodies