Evidence of early B-cell dysregulation in simian immunodeficiency virus infection: Rapid depletion of naïve and memory B-cell subsets with delayed reconstitution of the naïve B-cell population

David Kuhrt, Seth A. Faith, Amanda Leone, Mukta Rohankedkar, Donald L. Sodora, Louis Picker, Kelly Stefano Cole

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Despite eliciting a robust antibody response in humans, several studies in human immunodeficiency virus (HIV)-infected patients have demonstrated the presence of B-cell deficiencies during the chronic stage of infection. While several explanations for the HIV-induced B-cell deficit have been proposed, a clear mechanistic understanding of this loss of B-cell functionality is not known. This study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques to assess B-cell population dynamics beginning at the acute phase and continuing through the chronic phase of infection. Flow cytometric assessment demonstrated a significant early depletion of both naïve and memory B-cell subsets in the peripheral blood, with differential kinetics for recovery of these populations. Furthermore, the altered numbers of naïve and memory B-cell subsets in these animals corresponded with increased B-cell activation and altered proliferation profiles during the acute phase of infection. Finally, all animals produced high titers of antibody, demonstrating that the measurement of virus-specific antibody responses was not an accurate reflection of alterations in the B-cell compartment. These data indicate that dynamic B-cell population changes in SIV-infected macaques arise very early after infection at the precise time when an effective adaptive immune response is needed.

Original languageEnglish (US)
Pages (from-to)2466-2476
Number of pages11
JournalJournal of Virology
Volume84
Issue number5
DOIs
StatePublished - Mar 2010

Fingerprint

B-Lymphocyte Subsets
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Virus Diseases
B-lymphocytes
B-Lymphocytes
infection
Population
Infection
Antibody Formation
Human immunodeficiency virus
HIV
antibodies
Population Dynamics
Macaca
Adaptive Immunity
Macaca mulatta
Viruses
animals
population dynamics

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Evidence of early B-cell dysregulation in simian immunodeficiency virus infection : Rapid depletion of naïve and memory B-cell subsets with delayed reconstitution of the naïve B-cell population. / Kuhrt, David; Faith, Seth A.; Leone, Amanda; Rohankedkar, Mukta; Sodora, Donald L.; Picker, Louis; Cole, Kelly Stefano.

In: Journal of Virology, Vol. 84, No. 5, 03.2010, p. 2466-2476.

Research output: Contribution to journalArticle

Kuhrt, David ; Faith, Seth A. ; Leone, Amanda ; Rohankedkar, Mukta ; Sodora, Donald L. ; Picker, Louis ; Cole, Kelly Stefano. / Evidence of early B-cell dysregulation in simian immunodeficiency virus infection : Rapid depletion of naïve and memory B-cell subsets with delayed reconstitution of the naïve B-cell population. In: Journal of Virology. 2010 ; Vol. 84, No. 5. pp. 2466-2476.
@article{af7eb10714534ac5857a8aca86925fef,
title = "Evidence of early B-cell dysregulation in simian immunodeficiency virus infection: Rapid depletion of na{\"i}ve and memory B-cell subsets with delayed reconstitution of the na{\"i}ve B-cell population",
abstract = "Despite eliciting a robust antibody response in humans, several studies in human immunodeficiency virus (HIV)-infected patients have demonstrated the presence of B-cell deficiencies during the chronic stage of infection. While several explanations for the HIV-induced B-cell deficit have been proposed, a clear mechanistic understanding of this loss of B-cell functionality is not known. This study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques to assess B-cell population dynamics beginning at the acute phase and continuing through the chronic phase of infection. Flow cytometric assessment demonstrated a significant early depletion of both na{\"i}ve and memory B-cell subsets in the peripheral blood, with differential kinetics for recovery of these populations. Furthermore, the altered numbers of na{\"i}ve and memory B-cell subsets in these animals corresponded with increased B-cell activation and altered proliferation profiles during the acute phase of infection. Finally, all animals produced high titers of antibody, demonstrating that the measurement of virus-specific antibody responses was not an accurate reflection of alterations in the B-cell compartment. These data indicate that dynamic B-cell population changes in SIV-infected macaques arise very early after infection at the precise time when an effective adaptive immune response is needed.",
author = "David Kuhrt and Faith, {Seth A.} and Amanda Leone and Mukta Rohankedkar and Sodora, {Donald L.} and Louis Picker and Cole, {Kelly Stefano}",
year = "2010",
month = "3",
doi = "10.1128/JVI.01966-09",
language = "English (US)",
volume = "84",
pages = "2466--2476",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - Evidence of early B-cell dysregulation in simian immunodeficiency virus infection

T2 - Rapid depletion of naïve and memory B-cell subsets with delayed reconstitution of the naïve B-cell population

AU - Kuhrt, David

AU - Faith, Seth A.

AU - Leone, Amanda

AU - Rohankedkar, Mukta

AU - Sodora, Donald L.

AU - Picker, Louis

AU - Cole, Kelly Stefano

PY - 2010/3

Y1 - 2010/3

N2 - Despite eliciting a robust antibody response in humans, several studies in human immunodeficiency virus (HIV)-infected patients have demonstrated the presence of B-cell deficiencies during the chronic stage of infection. While several explanations for the HIV-induced B-cell deficit have been proposed, a clear mechanistic understanding of this loss of B-cell functionality is not known. This study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques to assess B-cell population dynamics beginning at the acute phase and continuing through the chronic phase of infection. Flow cytometric assessment demonstrated a significant early depletion of both naïve and memory B-cell subsets in the peripheral blood, with differential kinetics for recovery of these populations. Furthermore, the altered numbers of naïve and memory B-cell subsets in these animals corresponded with increased B-cell activation and altered proliferation profiles during the acute phase of infection. Finally, all animals produced high titers of antibody, demonstrating that the measurement of virus-specific antibody responses was not an accurate reflection of alterations in the B-cell compartment. These data indicate that dynamic B-cell population changes in SIV-infected macaques arise very early after infection at the precise time when an effective adaptive immune response is needed.

AB - Despite eliciting a robust antibody response in humans, several studies in human immunodeficiency virus (HIV)-infected patients have demonstrated the presence of B-cell deficiencies during the chronic stage of infection. While several explanations for the HIV-induced B-cell deficit have been proposed, a clear mechanistic understanding of this loss of B-cell functionality is not known. This study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques to assess B-cell population dynamics beginning at the acute phase and continuing through the chronic phase of infection. Flow cytometric assessment demonstrated a significant early depletion of both naïve and memory B-cell subsets in the peripheral blood, with differential kinetics for recovery of these populations. Furthermore, the altered numbers of naïve and memory B-cell subsets in these animals corresponded with increased B-cell activation and altered proliferation profiles during the acute phase of infection. Finally, all animals produced high titers of antibody, demonstrating that the measurement of virus-specific antibody responses was not an accurate reflection of alterations in the B-cell compartment. These data indicate that dynamic B-cell population changes in SIV-infected macaques arise very early after infection at the precise time when an effective adaptive immune response is needed.

UR - http://www.scopus.com/inward/record.url?scp=77649197874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649197874&partnerID=8YFLogxK

U2 - 10.1128/JVI.01966-09

DO - 10.1128/JVI.01966-09

M3 - Article

C2 - 20032183

AN - SCOPUS:77649197874

VL - 84

SP - 2466

EP - 2476

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 5

ER -