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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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