HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goodyear, C. S. Articles by Silverman, G. J. Search for Related Content PubMed PubMed Citation Articles by Goodyear, C. S. Articles by Silverman, G. J.

In Vivo V_L-Targeted Activation-Induced Apoptotic Supraclonal Deletion by a Microbial B Cell Toxin¹

Rheumatic Disease Core Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093

To interfere with host immune responses, some microbial pathogens produce proteins with the properties of superantigens, which can interact via conserved V region framework subdomains of the Ag receptors of lymphocytes rather than the complementarity-determining region involved in the binding of conventional Ags. In recent studies, we have elucidated how a model B cell superantigen affects the host immune system by targeting a conserved V_H site on the Ag receptors of B lymphocytes. To determine whether these findings represent a general paradigm, we investigated the in vivo immunobiologic properties of protein L of Peptostreptococcus magnus (PpL), a microbial Ig-binding protein specific for a V region site on Ig L chains. Our studies confirmed that PpL binding is restricted to a subset of murine V-expressing B cells, and found that B cells with stronger PpL-binding activity are associated with certain B cell subsets: splenic marginal zone (CD21^high CD23^low), splenic CD1⁺, peritoneal B-1a (IgD^low CD5⁺), and CD21^high CD24^high B cells in peripheral lymph nodes, mesenteric lymph nodes, and Peyer’s patches. Infusion of PpL triggered a sequence of events in B cell receptor (BCR)-targeted B cells, with rapid down-regulation of BCR, the induction of an activation phenotype, and limited rounds of proliferation. Apoptosis followed through a process heralded by the dissipation of mitochondrial membrane potential, the induction of the caspase pathway, DNA fragmentation, and the deposition of B cell apoptotic bodies. These studies define a common pathway by which microbial toxins that target V region-associated BCR sites induce programmed cell death.

This article has been cited by other articles:

				J. Jendholm, M. Samuelsson, L.-O. Cardell, A. Forsgren, and K. Riesbeck Moraxella catarrhalis-dependent tonsillar B cell activation does not lead to apoptosis but to vigorous proliferation resulting in nonspecific IgM production J. Leukoc. Biol., June 1, 2008; 83(6): 1370 - 1378. [Abstract] [Full Text] [PDF]

				I. Bekeredjian-Ding, S. Inamura, T. Giese, H. Moll, S. Endres, A. Sing, U. Zahringer, and G. Hartmann Staphylococcus aureus Protein A Triggers T Cell-Independent B Cell Proliferation by Sensitizing B Cells for TLR2 Ligands J. Immunol., March 1, 2007; 178(5): 2803 - 2812. [Abstract] [Full Text] [PDF]

				C. S. Goodyear and G. J. Silverman Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes PNAS, August 3, 2004; 101(31): 11392 - 11397. [Abstract] [Full Text] [PDF]