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Infection and Immunity, July 2007, p. 3354-3360, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00422-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Marginal Zone B-Cell Depletion Impairs Murine Host Defense against Borrelia burgdorferi Infection{triangledown}

Alexia A. Belperron, Catherine M. Dailey, Carmen J. Booth, and Linda K. Bockenstedt*

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520

Received 22 March 2007/ Accepted 12 April 2007

Marginal zone B (MZB) cells are a B-cell subset that produces T-cell-independent antibodies to blood-borne antigens. In this study, we examined the effects of MZB cell depletion on the immune response to the Lyme disease spirochete Borrelia burgdorferi, an extracellular pathogen for which T-cell-independent antibody is an important host defense. MZB cell depletion of C3H/HeJ mice using monoclonal antibody to LFA-1 and {alpha}4ß1 integrins reduced B. burgdorferi-specific immunoglobulin M (IgM) titers, enhanced pathogen burden, and led to more severe arthritis assessed within the first 2 weeks of infection. In addition, MZB cell-depleted mice had reduced levels of B. burgdorferi-specific IgG, which correlated with diminished splenic CD4+ T-cell-activation, proliferation, and cytokine production. Passive transfer of immune mouse serum from infected control mice into infected MZB cell-depleted mice reduced pathogen burden but did not alter the expression of T-cell activation markers on splenic CD4+ T cells. These findings demonstrate that MZB cells not only are a source of pathogen-specific IgM important for limiting spirochete burden and pathology but also play a prominent role in the priming of splenic T-cell responses to a blood-borne pathogen.

* Corresponding author. Mailing address: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, P.O. Box 208031, New Haven, CT 06520. Phone: (203) 785-2453. Fax: (203) 785-7053. E-mail: linda.bockenstedt{at}yale.edu

{triangledown} Published ahead of print on 30 April 2007.

Editor: D. L. Burns

Infection and Immunity, July 2007, p. 3354-3360, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00422-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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