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The Journal of Immunology, 2008, 181, 4043-4051
Copyright © 2008 by The American Association of Immunologists, Inc.
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Editing Antigen Presentation: Antigen Transfer between Human B Lymphocytes and Macrophages Mediated by Class A Scavenger Receptors1

Bohdan P. Harvey, Timothy E. Quan, Benjamin J. Rudenga, Robert M. Roman, Joe Craft and Mark J. Mamula2

Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520

B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated by B cell APCs. This finding led us to identify a process in mice whereby Ag-specific B cells transfer Ag to other APCs. In this study, we report the ability and mechanism by which human B lymphocytes can transfer BCR-captured Ag to macrophages. The transfer of Ag involves direct contact between the two cells followed by the capture of B cell-derived membrane and/or intracellular components by the macrophage. These events are abrogated by blocking scavenger receptor A, a receptor involved in the exchange of membrane between APCs. Macrophages acquire greater amounts of Ag in the presence of specific B cells than in their absence. This mechanism allows B cells to amplify or edit the immune response to specific Ag by transferring BCR-captured Ag to other professional APCs, thereby increasing the frequency of its presentation. Ag transfer may perpetuate chronic autoimmune responses to specific self-proteins and help explain the efficacy of B cell-directed therapies in human disease.

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 These studies were supported by National Institutes of Health Grants AI-48120 and AR-41032. B.P.H. was supported by an Arthritis Foundation postdoctoral fellowship.

2 Address correspondence and reprint requests to Dr. Mark J. Mamula, Yale University School of Medicine, 300 Cedar Street, The Anylan Center S515, P.O. Box 208031, New Haven, CT 06520-8031. E-mail address: mark.mamula{at}yale.edu

3 Abbreviations used in this paper: DC, dendritic cell; AF488, Alexa Fluor 488; anti-Ig, anti-human IgG/M F(ab')2; 2-APB, 2-aminoethyl diphenylborinate; B-LCL, B lymphoblastoid cell line; CTFR, CellTrace Far Red; CTO, CellTracker Orange; FSC, forward scatter; MFI, mean fluorescence intensity; PCC, pigeon cytochrome c; SR-A, class A scavenger receptor; SSC, side scatter.


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The JI 2008 181: 3729-3730. [Full Text]  





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