The Hierarchical Process of Differentiation of Long-Lived Antibody-Secreting Cells Is Dependent on Integrated Signals Derived from Antigen and IL-17A

Autor(es)

Grund, Lidiane Zito ^[1] ; Lopes-Ferreira, Monica ^[1] ; Lima, Carla ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Butantan Inst, Special Lab Appl Toxinol CEPID FAPESP, Immunoregulat Unit, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 9 SEP 18 2013.
• Citações Web of Science: 5

Resumo

Switched CD19-positive memory B cells purified from mice with chronic immune response against Thalassophryne nattereri 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. (AU)

• Processo FAPESP: 09/53078-1 - Influencia das celulas t na diferenciacao e manutencao de celulas b de memoria produtoras de anticorpos de longa vida (asc) induzidas durante a respota imune cronica ao veneno de thalassophryne nattereri
• Beneficiário: Lidiane Zito Grund
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/50001-0 - Efeito antiflamatorio das natterinas e do peptideo tnp,isolado do veneno de thalassophryne nattereri,em um modelo de encefalomielite autoimune experimental.
• Beneficiário: Carla Lima da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular