Enhancement and suppression of signaling by the conserved tail of IgG memory–type B cell antigen receptors
Autor: | Stephen Martin, Sarah L. Pogue, Karlee Silver, Christopher C. Goodnow, Kaiman Peng, Kiyoshi Takatsu, Keisuke Horikawa |
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Rok vydání: | 2007 |
Předmět: |
Transcriptional Activation
Sialic Acid Binding Ig-like Lectin 2 Cellular differentiation Immunology B-cell receptor Receptors Antigen B-Cell Biology Plasma cell Article Immunoglobulin G Mice 03 medical and health sciences 0302 clinical medicine Plasma cell differentiation Marginal zone B-cell medicine Animals Immunology and Allergy Extracellular Signal-Regulated MAP Kinases Phosphotyrosine Conserved Sequence B cell 030304 developmental biology Mice Knockout B-Lymphocytes 0303 health sciences Gene Expression Profiling Receptors IgG Cell Differentiation Articles Molecular biology Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Immunoglobulin M biology.protein Calcium Signal transduction Immunologic Memory Signal Transduction 030215 immunology |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
Popis: | Immunological memory is characterized by heightened immunoglobulin (Ig) G antibody production caused in part by enhanced plasma cell formation conferred by conserved transmembrane and cytoplasmic segments in isotype-switched IgG B cell receptors. We tested the hypothesis that the IgG tail enhances intracellular B cell antigen receptor (BCR) signaling responses to antigen by analyzing B cells from Ig transgenic mice with IgM receptors or chimeric IgMG receptors containing the IgG tail segment. The IgG tail segment enhanced intracellular calcium responses but not tyrosine or extracellular signal–related kinase (ERK) phosphorylation. Biochemical analysis and crosses to CD22-deficient mice established that IgG tail enhancement of calcium and antibody responses, as well as marginal zone B cell formation, was not due to diminished CD22 phosphorylation or inhibitory function. Microarray profiling showed no evidence for enhanced signaling by the IgG tail for calcium/calcineurin, ERK, or nuclear factor κB response genes and little evidence for any enhanced gene induction. Instead, almost half of the antigen-induced gene response in IgM B cells was diminished 50–90% by the IgG tail segment. These findings suggest a novel “less-is-more” hypothesis to explain how switching to IgG enhances B cell memory responses, whereby decreased BCR signaling to genes that oppose marginal zone and plasma cell differentiation enhances the formation of these key cell types. |
Databáze: | OpenAIRE |
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