Galectin-1 and Galectin-8 Have Redundant Roles in Promoting Plasma Cell Formation

Abstract

Galectin (Gal) family members are a type of soluble lectin, and they play important roles in immunomodulation. Their redundant roles have been proposed. We previously found that Gal-1 promotes the formation of Ab-secreting plasma cells, but B cells from Gal-1–deficient and control animals produce comparable amounts of Abs. In the current study, we used synthetic sulfomodified N-acetyllactosamine (LacNAc) analogs and short hairpin RNAs for Gal-8 to demonstrate a redundancy in the effects of Gal-1 and Gal-8 on plasma cell formation. Gal-1 and Gal-8 were both expressed during plasma cell differentiation, and both Gals promoted the formation of plasma cells. Gal-1 and Gal-8 bound better to mature B cells than to plasma cells, and the expression of glycosyltransferase enzymes changed during differentiation, with a decrease in mannosyl (α-1,6-)-glycoprotein β-1,6-N-acetyl-glucosaminyltransferase and N-acetylglucosaminyltransferase-1 mRNAs in plasma cells. Synthetic sulfomodified Galβ1-3GlcNAc disaccharides (type 1 LacNAcs) selectively prevented Gal-8 binding, leading to a blockade of Ab production in Gal-1–deficient B cells. Furthermore, synthetic type 1 LacNAcs that were able to block the binding of both Gals greatly reduced the effect of exogenously added recombinant Gal-1 and Gal-8 on promoting Ab production. These results reveal a novel role for Gal-8 in collaboration with Gal-1 in plasma cell formation, and suggest the possibility of using distinct LacNAc ligands to modulate the function of Gals.

Redundant and Antagonistic Functions of Galectin-1, -3, and -8 in the Elicitation of T Cell Responses

“…Tribulatti, and O. Campetella, unpublished observations). With regard to B cells, it was reported that both Gal-1 and Gal-8, but not Gal-3, promoted plasma cell differentiation (39), probably contributing to the humoral response as well. Nevertheless, we cannot discount a direct effect of Gals on naive T cells during the Ag response in vivo, because Gal-8 was demonstrated to induce purified CD4 T cell proliferation (13) and, as described in this article, chimeric Gal-1-8-1 also induced splenocyte proliferation.…”

B-cell maturation antigen is modified by a single N -glycan chain that modulates ligand binding and surface retention

“…Given that the cell surface of murine plasma cells displayed increased sialylation compared with the stimulated murine mature B cells (28) and that BCMA could be labeled by ManNAcyne, we next examined the sialosides linkage of BCMA on MM cells. Sambucus nigra lectin (SNA), which preferentially binds to the α2-6-linked sialosides, and Maackia amurensis lectin (MAL), which selectively binds to the α2-3-linked sialosides, can bind to H929 and RPMI8226 cells as determined by flow cytometry analysis, but the binding was significantly reduced on cells pretreated with sialidase, which hydrolyzes the α2-3-and α2-6-linked sialosides ( Fig.…”

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

“…Once activated, T cells undergo apoptosis in response to Gal-8, involving an enhanced expression of FasL receptor (Norambuena et al, 2009). In B cells, Gal-8 promotes diff erentiation toward plasma cells (Tsai et al, 2011), while neutrophils respond to this lectin by activating their plasma membrane NADPH-oxidase (Nishi et al, 2003). There is also evidence suggesting an altered Gal-8 function in rheumatic, autoimmune and infl ammatory disorders (Nishi et al, 2003;Eshkar Sebban et al, 2007).…”

“…In the immune system Gal-8 can play important roles in the homeostasis of T- Tribulatti et al, 2007;Norambuena et al, 2009;Tribulatti et al, 2009;Tribulatti et al, 2012) and B-cells (Tsai et al, 2011). Gal-8 expression in the thymus and its pro-apoptotic eff ects on CD4 high CD8 high thymocytes suggest a role in shaping the T cell repertoire (Tribulatti et al, 2007).…”