Lack of galectin-3 modifes diferentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell diferentiation

Resumo

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 diferentiation 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 diferentiation in the bone marrow (BM) and spleen. The BM of gal-3-defcient 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 signifcantly increased in the BM and blood of Lgals3−/− mice. For the frst time, we demonstrated that gal-3 inhibits Notch signaling activation in lymphoid organs regulating earlier and terminal events of B cell diferentiation.

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OLIVEIRA, Felipe Leite de et al. Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation. Scientific Reports, London, v. 8, e3495, 2018. DOI: 10.1038/s41598-018-21409-7. Disponível em: https://www.nature.com/articles/s41598-018-21409-7. Acesso em: 21 jan. 2025.