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Title: | Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation |
Authors: | OLIVEIRA, Felipe Leite de; SANTOS, Sofia Nascimento dos; RICON, Lauremilia; COSTA, Thayse Pinheiro da; PEREIRA, Jonathas Xavier; BRAND, Camila; FERMINO, Marise Lopes; CHAMMAS, Roger; BERNARDES, Emerson Soares; EL-CHEIKH, Marcia Cury |
Citation: | SCIENTIFIC REPORTS, v.8, article ID 3495, 14p, 2018 |
Abstract: | Galectin-3 (Gal-3) is a beta-galactoside binding protein that controls cell-cell and cell-extracellular matrix interactions. In lymphoid organs, gal-3 inhibits B cell differentiation by mechanisms poorly understood. The B cell development is dependent on tissue organization and stromal cell signaling, including IL-7 and Notch pathways. Here, we investigate possible mechanisms that gal-3 interferes during B lymphocyte differentiation in the bone marrow (BM) and spleen. The BM of gal-3-deficient mice (Lgals3(-/-)mice) was evidenced by elevated numbers of B220(+)CD19(+)c-Kit(+)IL-7R(+) progenitor B cells. In parallel, CD45-bone marrow stromal cells expressed high levels of mRNA IL-7, Notch ligands (Jagged-1 and Delta-like 4), and transcription factors (Hes-1, Hey-1, Hey-2 and Hey-L). The spleen of Lgals3(-/-)mice was hallmarked by marginal zone disorganization, high number of IgM(+) IgD(+) B cells and CD138(+)plasma cells, overexpression of Notch ligands (Jagged-1, Delta-like 1 and Delta-like 4) by stromal cells and Hey-1. Morever, IgM(+) IgD(+) B cells and B220(+)CD138(+)CXCR4(+) plasmablasts were significantly increased in the BM and blood of Lgals3(-/-)mice. For the first time, we demonstrated that gal-3 inhibits Notch signaling activation in lymphoid organs regulating earlier and terminal events of B cell differentiation. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MDR Artigos e Materiais de Revistas Científicas - LIM/24 Artigos e Materiais de Revistas Científicas - ODS/03 |
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art_OLIVEIRA_Lack_of_galectin3_modifies_differentially_Notch_ligands_in_2018.PDF | publishedVersion (English) | 3.08 MB | Adobe PDF | View/Open |
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