Glycosylation of IgG B cell receptor (IgG BCR) in multiple myeloma: relationship between sialylation and the signal activity of IgG BCR

Abstract

Little is known about the glycosylation of the isotype switched B cell receptor (BCR) in multiple myeloma, and the way it might affect receptor function. In this work IgG BCRs isolated from the individual lysates of peripheral blood lymphocytes (PBL) of 32 patients with IgG multiple myeloma and healthy controls were investigated for the expression of sialic acid (SA), galactose (Gal) and N-acetylglucosamine (GlcNAc), the sugars known to specify the glycoforms of human serum IgG. The degree of glycosylation and signaling status of all 32 isolated myeloma IgG BCRs were correlated and compared with the glycosylation of the IgG paraproteins isolated from sera of the same patients. It was shown that BCR IgG in myeloma is more heavily sialylated when compared with normal controls, that the increased sialylation of IgG BCR is associated with higher levels of tyrosine phosphorylation (signaling activity) of the IgG BCR supramolecular complex and that BCR IgG and serum IgG paraprotein from the same patient differed in all cases in the levels of terminal sugar expression. The results suggest that the development of the malignant clone in MM from post-switch B cells expressing IgG BCR at their surfaces to plasma cells secreting IgG paraprotein may be followed by permanent glycosylation changes in the IgG molecules.

Characteristics of BAFF and APRIL factor expression in multiple myeloma and clinical significance

“…With ELISA, Ilić et al analyzed the average concentration of BAFF level in 51 patients with myeloma patients and 11 normal people. The result was 968 and 417 pg/ml, respectively, which was statistically different ( 16 ).…”

Roles for major histocompatibility complex glycosylation in immune function

“…In both studies, the role for N -glycans could not be attributed to changes in the relative surface expression of cell surface MHCII, but these results must be considered in the context of the experimental systems utilized. Transformed antigen presenting cell lines and the responding T hybridomas, due to their malignant nature, can have significant differences in N -glycosylation patterns than that of their primary cell counterparts [76, 77]. In fact, aberrant glycosylation patterns are hallmarks of many cancer cell glycoproteins [78, 79] that are targets in ongoing cancer vaccination efforts [80–82].…”

Glyco‐biomarkers: Potential Determinants of Cellular Physiology and Pathology

“…Examples include galectin 1 which induces T cell apoptosis and galectin 3, associated with tumours, which inhibits apoptosis collectins, adhesion molecules, and anti-carbohydrate antibodies (Table 1) [8][9][10][11][12]. This versatile carbohydrate recognition system combined with our extensive glycome are key players in orchestrating the complex functional network of bimolecular interactions that coordinate molecular and cellular function in relation to innate and adaptive immunity [13][14][15][16][17][18][19]. Given the diversity of structures and functions, and the potential for conveying information essential to maintenance of immune homeostasis, it is not surprising that the role of glycosylation in the development, regulation, and progression of disease has come under increased scrutiny [6].…”