Abstract
Switched CD19-positive memory B cells purified from mice with chronic immune response against Thalassophrynenattereri venom proteins were cultured with venom or cytokines. Our results confirm the existence of a hierarchic process of differentiation: activated memory B cells progressively acquire increasing levels of CD138 and decreasing levels of CD45R/B220 to finally arrive at ASC with B220(neg) phenotype, which are IgG1-secreting cells. Only Bmem from peritoneal cavity or bone marrow of VTn immunized mice presented the capacity to generate ASC functionally active. IL-17A or IL-21/IL-23/IL-33 improves the ability of venom to induce intracellular IgG of peritoneal derived-ASC. Cognate stimulation with venom and IL-17A is sufficient to down-regulate the expression of CD45R/B220. BAFF-R is up-regulated in splenic or medullar derived-ASC stimulated by venom, CpG or cytokines. Only splenic derived-ASC up-regulate Bcl-2 expression after CpG or the combination of IL-21/IL-23/IL-33 stimulation. Finally, the activation of ASC for IgG1 secretion is triggered by venom proteins in peritoneal cavity and by IL-17A in medullar niche. These results show the importance of the integration of signals downstream of BCR and IL17-A receptors in modulating ASC differentiation, focusing in the microenvironment niche of their generation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody-Producing Cells / cytology*
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Antibody-Producing Cells / drug effects
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Antibody-Producing Cells / metabolism
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Antigens / immunology*
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Antigens, CD19 / metabolism
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Apoptosis / drug effects
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Apoptosis / immunology
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B-Cell Activation Factor Receptor / metabolism
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B-Lymphocytes / immunology
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Cell Differentiation / drug effects
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Cell Differentiation / immunology*
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Cell Membrane / metabolism
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Fish Venoms / immunology
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Immunoglobulin G / biosynthesis
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Immunologic Memory / drug effects
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Interleukin-17 / metabolism*
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Interleukin-23 / pharmacology
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Interleukins / pharmacology
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Leukocyte Common Antigens / metabolism
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Lymphocyte Count
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Male
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Mice
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Recombinant Proteins / pharmacology
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Signal Transduction* / drug effects
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Signal Transduction* / immunology
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Spleen / cytology
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Toll-Like Receptor 9 / metabolism
Substances
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Antigens
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Antigens, CD19
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B-Cell Activation Factor Receptor
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Fish Venoms
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Immunoglobulin G
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Interleukin-17
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Interleukin-23
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Interleukins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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Tlr9 protein, mouse
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Toll-Like Receptor 9
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Leukocyte Common Antigens
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interleukin-21
Grants and funding
This work was supported by FAPESP 2012/50001-0 and 2009/53078-1 CNPQ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.