Lack of Galectin-3 Disturbs Mesenteric Lymph Node Homeostasis and B Cell Niches in the Course of Schistosoma mansoni Infection

Abstract

Galectin-3 is a β-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3-/- mice. Schistosoma mansoni synthesizes GalNAcβ1-4(Fucα1-3)GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine β1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3-/- mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V+/PI- cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in non-lymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S.mansoni.

Galectin-3 in autoimmunity and autoimmune diseases

“…[22][23][24] Moreover, gal-3 inhibits B-cell differentiation into plasma cells in distinct lymphoid tissues, [23][24][25] plays anti-apoptotic functions on proliferative B-cell neoplasms 26 and maintains B-cell anergy. 27 The advent of gal-3 deficient mice (gal-3 À/À mice) allowed more detailed studies on immunomodulatory mechanisms of gal-3.…”

“…24,31,32 Gal-3 À/À mice have an intense plasmacytogenesis and hypergammaglobulinemia as well as follicular B cells highly susceptible to apoptotic stimuli. [22][23][24] In addition, autoantibody transgenic mice lacking gal-3 (and also gal-1) have spontaneous anti-laminin-secreting plasma cell differentiation in the spleen followed by B-cell depletion and anergy. 27 These data suggest that gal-3 plays a central role in maintaining B-cell tolerance.…”

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

“…Subsequently, we demonstrated that S. mansoni-infected Lgals3 −/− mice have hyperglobulinemia and intense plasmacytogenesis in the bone marrow, mesenteric lymph nodes and spleen (Brand et al 2012;Oliveira et al 2007Oliveira et al , 2011. Here, we propose a new regulatory role for galectin-3 in IgA + plasma cell differentiation in the peritoneal cavity during chronic schistosomiasis inflammation and during IL-5 and TGF-β1 treatment in vitro and in vivo.…”

“…Immediately after extirpation, the omentum was fixed for 24 h in 10 % buffered formalin, dehydrated and embedded in paraffin. Tissue sections (5 μm thick) were stained with hematoxilin and eosin or processed for further immunohistochemistry analysis (Oliveira et al 2011). The tissue was analyzed by a light microscope (Zeiss-Axioplan, Jena, Germany) and images were acquired by bright field microscopy via a camera (Evolution MP 5.0 RTV-Color-Media Cybernetics, Canada).…”

“…Galectin-3 is highly expressed by liver cells located around the intrahepatic granulomas during chronic schistosomiasis. Recently, we demonstrated that S. mansoniinfected Lgals3 −/− mice exhibit abnormal plasmacytosis in the bone marrow, mesenteric lymph nodes and spleen followed by significant hyperglobulinemia (Brand et al 2012;Oliveira et al 2007Oliveira et al , 2011. However, the involvement of galectin-3 in B cell physiology is far from being completely understood and only a few reports in the literature address the role of galectin-3 on B cell activation/differentiation.…”