Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation
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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.
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OLIVEIRA, FELIPE L. de; SANTOS, SOFIA N. dos; RICON, LAUREMILIA; COSTA, THAYSE P. da; PEREIRA, JONATHAS X.; BRAND, CAMILA; FERMINO, MARISE L.; CHAMMAS, ROGER; BERNARDES, EMERSON S.; EL-CHEIKH, MARCIA C. Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation. Scientific Reports, v. 8, n. 3495, p. 1-14, 2018. DOI: 10.1038/s41598-018-21409-7. Disponível em: http://repositorio.ipen.br/handle/123456789/28980. Acesso em: 30 Dec 2025.
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