title: The Bacterial Enzyme IdeS Cleaves the IgG-Type of B Cell Receptor (BCR), Abolishes BCR-Mediated Cell Signaling, and Inhibits Memory B Cell Activation.
abstract: Ag binding to the BCR is a critical step in B cell development and activation, initiating a cascade of signaling events ultimately leading to proliferation, differentiation, or cell death. A bacterial enzyme, IgG-degrading enzyme of Streptococcus pyogenes (IdeS), was shown to specifically cleave IgG molecules below the hinge region of soluble IgG and when IgG is bound to Ag, resulting in one F(ab')2 molecule and one homodimeric Fc fragment. Whether IdeS could also cleave the IgG molecule when it is present in the BCR attached to the B cell membrane in a complex with CD79a and CD79b is unknown. In this article, we present human in vitro and ex vivo data showing that IdeS cleaves the IgG present in the BCR complex and very efficiently blocks Ag binding to the BCR. As a consequence of IdeS cleaving the BCR, signaling cascades downstream of the BCR are blocked, and memory B cells are temporarily silenced, preventing them from responding to antigenic stimulation and their transition into Ab-producing cells.
authors.affiliation: Hansa Medical AB, SE-22007 Lund, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Järnum
authors.affiliation: Hansa Medical AB, SE-22007 Lund, Sweden.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0002-8294-8991
authors.initials: R
authors.lastname: Bockermann
authors.affiliation: Hansa Medical AB, SE-22007 Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Runström
authors.affiliation: Hansa Medical AB, SE-22007 Lund, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Winstedt
authors.affiliation: Hansa Medical AB, SE-22007 Lund, Sweden christian.kjellman@hansamedical.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Kjellman
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007156:Immunologic Memory; D056747:Immunomodulation; D008213:Lymphocyte Activation; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013297:Streptococcus pyogenes / Q000201:enzymology*
chemical_list: D000941:Antigens; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus; D011947:Receptors, Antigen, B-Cell