title: High-affinity B cell receptor ligation by cognate antigen induces cytokine-independent isotype switching.
abstract: The selection of an appropriate Ig isotype is critical for an effective immune response against pathogens. Isotype regulation is sensitive to external signals, particularly cytokines secreted by Th cells. For example, IL-4 induces isotype switching to IgG1 via a STAT6-dependent signaling pathway. In this study, we show that BCR ligation also induces IgG1 switching in mouse B cells. The extent of switch induction by Ag is affinity-dependent, and high-affinity Ag binding leads to IgG1 switching levels comparable to those induced by saturating IL-4. However, the Ag-induced IgG1 switch does not require additional cytokine signals and occurs in a STAT6-independent manner. Thus, BCR ligation represents a novel pathway for direct isotype switching leading to IgG1 secretion.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Turner
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Corcoran
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000941:Antigens; D011947:Receptors, Antigen, B-Cell; C421864:hen egg lysozyme; D009113:Muramidase