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PMID: 19582166 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

PLoS medicine ·Vol. 6 ·No. 7 ·2009-07-07 ·Pages e1000107

Levesque MC, Moody MA, Hwang KK, Marshall DJ, Whitesides JF, Amos JD, Gurley TC, Allgood S, Haynes BB, Vandergrift NA, Plonk S, Parker DC, Cohen MS, Tomaras GD, Goepfert PA, Shaw GM, Schmitz JE, Eron JJ, Shaheen NJ, Hicks CB, Liao HX, Markowitz M, Kelsoe G, Margolis DM, Haynes BF

Abstract

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.

MeSH Terms
Adolescent Adult Antibodies, Viral/blood Apoptosis/immunology Autoimmunity B-Lymphocytes/metabolism Cell Differentiation/immunology Female Germinal Center/pathology,virology HIV Antibodies/blood HIV Infections/immunology HIV-1/immunology Humans Ileum/immunology,pathology,virology Influenza, Human/immunology Lymphocyte Activation Male Middle Aged Peyer's Patches/pathology,virology Time Factors Young Adult
Chemicals
Antibodies, Viral HIV Antibodies
Authors & Affiliations
25 authors, click to expand affiliations / ORCID
Levesque Marc C
Department of Medicine, Duke University School of Medicine, Durham, North Carolina, United States of America.
Moody M Anthony
Hwang Kwan-Ki
Marshall Dawn J
Whitesides John F
Amos Joshua D
Gurley Thaddeus C
Allgood Sallie
Haynes Benjamin B
Vandergrift Nathan A
Plonk Steven
Parker Daniel C
Cohen Myron S
Tomaras Georgia D
Goepfert Paul A
Shaw George M
Schmitz Jörn E
Eron Joseph J
Shaheen Nicholas J
Hicks Charles B
Liao Hua-Xin
Markowitz Martin
Kelsoe Garnett
Margolis David M
Haynes Barton F
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Article Info
Journal
PLoS medicine
Abbr.
PLoS Med
ISSN
1549-1676
DOI
10.1371/journal.pmed.1000107
Published
2009-07-07
Epub
2009-00-07
Pages
e1000107
Language
English
Region
United States
NLM ID
101231360
PMCID
PMC2702159
Subset
IM
Grants
NIAID NIH HHS · P30 AI050410 · United States
NIAID NIH HHS · T32 AI007392 · United States
NIAID NIH HHS · U19 AI067854 · United States
External Links
PubMed source DOI: 10.1371/journal.pmed.1000107 PMC Full Text View journal details
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