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Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation.


ABSTRACT: Galectin-3 (Gal-3) is a ?-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.

SUBMITTER: de Oliveira FL 

PROVIDER: S-EPMC5823902 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation.

de Oliveira Felipe Leite FL   Dos Santos Sofia Nascimento SN   Ricon Lauremilia L   da Costa Thayse Pinheiro TP   Pereira Jonathas Xavier JX   Brand Camila C   Fermino Marise Lopes ML   Chammas Roger R   Bernardes Emerson Soares ES   El-Cheikh Márcia Cury MC  

Scientific reports 20180222 1


Galectin-3 (Gal-3) is a β-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  ...[more]

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