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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Grund, Lidiane Zito [1] ; Lopes-Ferreira, Monica [1] ; Lima, Carla [2]
Total Authors: 3
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: PLoS One; v. 8, n. 9 SEP 18 2013.
Web of Science Citations: 5
Abstract

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)