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Journal of Virology, July 2001, p. 6359-6366, Vol. 75, No. 14
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.14.6359-6366.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Hepatitis B Virus Core Antigen Binds and Activates
Naive Human B Cells In Vivo: Studies with a Human PBL-NOD/SCID
Mouse Model
Tinghua
Cao,1
Una
Lazdina,2
Isabelle
Desombere,1
Peter
Vanlandschoot,1
David R.
Milich,3
Matti
Sällberg,2 and
Geert
Leroux-Roels1,*
Center for Vaccinology, Department of Clinical Chemistry,
Microbiology and Immunology, Ghent University, Ghent,
Belgium1; Divisions of
Clinical Virology, F68, and Basic Oral Sciences, F58, Karolinska
Institute, Huddinge University Hospital, S-141 86 Huddinge,
Sweden2; and Vaccine Research Institute
of San Diego, San Diego, California3
Received 20 December 2000/Accepted 24 April 2001
The hepatitis B virus (HBV) core (HBc) antigen (HBcAg) is a highly
immunogenic subviral particle. Studies with mice have shown that HBcAg
can bind and activate B cells in a T-cell-independent fashion. By using
a human peripheral blood leukocyte
(hu-PBL)-Nod/LtSz-Prkdcscid/Prkdcscid
(NOD/SCID) mouse model, we show here that HBcAg also activates human B
cells in vivo in a T-cell-independent way. HBcAg was capable of
inducing the secretion of HBcAg-binding human immunoglobulin M (IgM) in
naive human B cells derived from adult human and neonatal (cord blood)
donors when these hu-PBL were transferred directly into the spleens of
optimally conditioned NOD/SCID mice. No such responses were found in
chimeric mice that were given hu-PBL plus HBV e antigen or hu-PBL plus
phosphate-buffered saline. In addition, HBcAg activated purified human
B cells to produce anti-HBc IgM in the chimeric mice, thus providing
evidence that HBcAg behaves as a T-cell-independent antigen in humans.
However, HBcAg-activated hu-PBL from naive donors were unable to switch
from IgM to IgG production, even after a booster dose of HBcAg.
Production of HBcAg-specific IgG could only be induced when hu-PBL from
subjects who had recovered from or had an ongoing chronic HBV infection were transferred into NOD/SCID mice. Our data suggest that humans also
have a population of naive B cells that can bind HBcAg and is
subsequently activated to produce HBcAg-binding IgM.
*
Corresponding author. Mailing address: Center for
Vaccinology, Department of Clinical Chemistry, Microbiology and
Immunology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent,
Belgium. Phone: 32 9 2403422. Fax: 32 9 2404985. E-mail:
geert.lerouxroels{at}rug.ac.be.
Journal of Virology, July 2001, p. 6359-6366, Vol. 75, No. 14
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.14.6359-6366.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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