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B Cell Receptor-Mediated Internalization of Salmonella: A Novel Pathway for Autonomous B Cell Activation and Antibody Production¹

Yuri Souwer^2,*,, Alexander Griekspoor^2,, Tineke Jorritsma^*, Jelle de Wit^*, Hans Janssen, Jacques Neefjes^3, and S. Marieke van Ham^3,*

^* Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

The present paradigm is that primary B cells are nonphagocytosing cells. In this study, we demonstrate that human primary B cells are able to internalize bacteria when the bacteria are recognized by the BCR. BCR-mediated internalization of Salmonella typhimurium results in B cell differentiation and secretion of anti-Salmonella Ab by the Salmonella-specific B cells. In addition, BCR-mediated internalization leads to efficient Ag delivery to the MHC class II Ag-loading compartments, even though Salmonella remains vital intracellularly in primary B cells. Consequently, BCR-mediated bacterial uptake induces efficient CD4⁺ T cell help, which boosts Salmonella-specific Ab production. BCR-mediated internalization of Salmonella by B cells is superior over extracellular Ag extraction to induce rapid and specific humoral immune responses and efficiently combat infection.

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 grants from the Dutch Cancer Society (Koningin Wilhelmina Fonds) (Grant NKI 2001-2415), the Landsteiner Foundation for Blood Research (Grant 0533), and The Netherlands Organization for Scientific Research (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek).

² Y.S. and A.G. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Jacques Neefjes, Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands and Dr. S. Marieke van Ham, Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands. E-mail addresses: j.neefjes{at}nki.nl and m.vanham{at}sanquin.nl

⁴ Abbreviations used in this paper: MIIC, MHC class II-containing compartment; SCV, Salmonella-containing vacuole; EM, electron microscopy; DAPI, 4',6- diamidino-2-phenylindole; LB, Luria-Bertani; SPI, Salmonella pathogenicity island; DC, dendritic cell.

⁵ The online version of this article contains supplemental material.