Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.
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.
Levesque
Marc C
MC
Department of Medicine, Duke University School of Medicine, Durham, North Carolina, United States of America.
Moody
M Anthony
MA
Hwang
Kwan-Ki
KK
Marshall
Dawn J
DJ
Whitesides
John F
JF
Amos
Joshua D
JD
Gurley
Thaddeus C
TC
Allgood
Sallie
S
Haynes
Benjamin B
BB
Vandergrift
Nathan A
NA
Plonk
Steven
S
Parker
Daniel C
DC
Cohen
Myron S
MS
Tomaras
Georgia D
GD
Goepfert
Paul A
PA
Shaw
George M
GM
Schmitz
Jörn E
JE
Eron
Joseph J
JJ
Shaheen
Nicholas J
NJ
Hicks
Charles B
CB
Liao
Hua-Xin
HX
Markowitz
Martin
M
Kelsoe
Garnett
G
Margolis
David M
DM
Haynes
Barton F
BF
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
D000914:Antibodies, Viral; D015483:HIV Antibodies