Lack of galectin-3 up-regulates IgA expression by peritoneal B1 lymphocytes during B cell differentiation

Abstract

Galectin-3 is a β-galactoside-binding protein with an inhibitory role in B cell differentiation into plasma cells in distinct lymphoid tissues. We use a model of chronic schistosomiasis, a well-characterized experimental disease hallmarked by polyclonal B cell activation, in order to investigate the role of galectin-3 in controlling IgA production through peritoneal B1 cells. Chronically infected, galectin-3-deficient mice (Lgals3 −/− ) display peritoneal fluid hypercellularity, increased numbers of atypical peritoneal IgM + /IgA + B1a and B1b lymphocytes and histological disturbances in plasma cell niches when compared with Lgals3 + / + mice. Similar to our infection model, peritoneal B1 cells from uninfected Lgals3 −/− mice show enhanced switching to IgA after in vitro treatment with interleukin-5 plus transforming growth factor-β (IL-5 + TGF-β1). A higher number of IgA + B1a lymphocytes was found in the peritoneal cavity of Lgals3 −/− -uninfected mice at 1 week after i.p. injection of IL-5 + TGF-β1; this correlates with the increased levels of secreted IgA detected in the peritoneal fluid of these mice after cytokine treatment. Interestingly, a higher number of degranulated mast cells is present in the peritoneal cavity of uninfected and Schistosoma mansoni-infected Lgals3 −/− mice, indicating that, at least in part, mast cells account for the enhanced differentiation of B1 into IgAproducing B cells found in the absence of galectin-3. Thus, a novel role is revealed for galectin-3 in controlling the expression of surface IgA by peritoneal B1 lymphocytes; this might have important implications for manipulating the mucosal immune response.

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

“…Gal-3 has been described as significant regulator of B cell differentiation 3 , 4 , 7 , 8 . However, the molecular and cellular mechanisms involved are poorly understood.…”

“…In non-conventional peritoneal B1 lymphocytes biology, gal-3 also plays regulatory roles in the differentiation of both B1a and B1b cells into plasma cells by IL-5 and Blimp-1 signaling-dependent manner 5 . Clearly, gal-3 interferes with B cell compartments in distinct lymphoid organs 4 – 8 . However, the mechanisms that correlate gal-3 with molecular pathways during bone marrow B lymphopoiesis, peripheral mobilization and settlement mainly in the spleen, are poorly understood.…”

The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation

“…An inhibitory role of galectin-3 was demonstrated in a model of galectin-3 knockout mouse, where B lymphocytes of the peritoneal cavity favored differentiating into plasma cells [ 153 ]. More specifically, a significant increase of IgA-producing cells in the peritoneal cavity was observed in comparison to galectin-3-expressing mice during chronic schistosomiasis as well as in response to interleukin-5 and transforming growth factor-β [ 154 ]. Although the mechanisms of galectin-3-dependent inhibition of B cell differentiation are obscure, a recent study revealed that Notch signaling pathways might play an important regulatory role [ 155 ].…”

Epigenetic Therapy as a Putative Molecular Target to Modulate B Cell Biology and Behavior in the Context of Immunological Disorders

“…In accordance, B1 cells may modulate their adhesion molecules and differentiate into plasma cells still in the peritoneal cavity. On the other hand, these cells can adhere to mesenteric membranes or omentum, as described in the literature, if previously activated by the absence of galectin-3 [26].…”

“…In addition to the constitutive expression of STAT3 by B1 cells, and in contrast to B2 cells, these cells also express the interleukin-5 receptor alpha (IL-R5α) chain, which renders to this subset the ability to specifically respond to interleukin 5 (IL-5), GM-CSF, and IL-3 [29]. In this way, B1 lymphocytes can be maintained in vitro if properly stimulated by IL-5 allowing the analysis of their behavior such as the proliferation rate, survival, and/or differentiation into Ig-producing cells and IgA switch under experimental conditions [26,30,31].…”