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Follicular and Marginal Zone B Cells Fail to Cross-Present MHC Class I-Restricted Epitopes Derived from Viral Particles¹

Cytos Biotechnology AG, Schlieren, Switzerland

Viruses and virus-like particles (VLPs) are known to be potent inducers of B cell as well as Th cell and CTL responses. It is well established that professional APCs such as dendritic cells (DCs) and macrophages efficiently process viral particles for both MHC class I- and MHC class II-associated presentation, which is essential for induction of CTL and Th cell responses, respectively. Less is known, however, about the ability of B cells to present epitopes derived from viral particles to T cells. Using two different VLPs, in this study we show in vitro as well as in vivo that DCs present VLP-derived peptides in association with MHC class I as well as class II. In contrast, although B cells were able to capture VLPs similarly as DCs and although they efficiently processed VLPs for presentation in association with MHC class II, they failed to process exogenous VLPs for presentation in association with MHC class I. Thus, in contrast to DCs, B cells are not involved in the process of cross-priming. This finding is of physiological importance because B cells with the ability to cross-present Ag to specific CD8⁺ T cells may be killed by these cells, preventing the generation of neutralizing Ab responses.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funding under the Sixth Research Framework Program of the European Union, Project MUGEN (MUGEN LSHG-CT-2005-005203).

² Address correspondence and reprint requests to Dr. Martin F. Bachmann, Cytos Biotechnology AG, Wagistrasse 25, CH-8952 Schlieren, Switzerland. E-mail address: martin.bachmann{at}cytos.com

³ Abbreviations used in this paper: VLP, virus-like particle; DC, dendritic cell; FCM, flow cytometry; FO, follicular; HBcAg, hepatitis B core Ag; MZ, marginal zone.