Scientific Reports (Feb 2018)

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

  • Felipe Leite de Oliveira,
  • Sofia Nascimento dos Santos,
  • Lauremilia Ricon,
  • Thayse Pinheiro da Costa,
  • Jonathas Xavier Pereira,
  • Camila Brand,
  • Marise Lopes Fermino,
  • Roger Chammas,
  • Emerson Soares Bernardes,
  • Márcia Cury El-Cheikh

DOI
https://doi.org/10.1038/s41598-018-21409-7
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 14

Abstract

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Abstract 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 (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.