Galectin-Glycan Interactions as Regulators of B Cell Immunity

Giovannone, Nicholas; Smith, Logan K.; Treanor, Bebhinn; Dimitroff, Charles J.

doi:10.3389/fimmu.2018.02839

Cited by 42 publications

(22 citation statements)

References 74 publications

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“…Using a soluble recombinant version of CD22 (CD22-Fc), Nitschke and co-workers identified sialylated ligands of CD22 are expressed on sinusoidal endothelial cells (ECs) in the bone marrow [117]. Administration of anti-mouse CD22 antibodies or CD22-Fc block CD22 ligand interactions, resulting in reduced migration of mature B cells in bone marrow by approximately 50 percent, recapitulating the observations from other studies using CD22-deficient mouse models [81], [118]. Furthermore, adoptive transfer of WT B cells into St6gal1 knockout mice resulted in a diminished capacity of B cells to home in the bone marrow.…”

Section: Beyond Regulation Of the Bcr: Other Roles For Cd22 In Contromentioning

confidence: 53%

“…5]. In the absence of ligands, CD22 is more able to co-localize with the BCR, which could be the consequence of three effects: (1) protein–protein interactions [80]; (2) hetero-dimerization by galectins [81]; or (3) increase mobility https://www.zotero.org/google-docs/?KaqFiD [37]. In the presence of ligands, nanoclusters of CD22 effectively maintain CD22 away from the BCR [Fig.…”

Section: Roles Of Glycan Ligands In Controlling Cd22 As a Bcr Inhibitmentioning

confidence: 99%

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Coordinated roles for glycans in regulating the inhibitory function of CD22 on B cells

2019

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CD22 is an inhibitory B cell co-receptor that recognizes sialic acid-containing glycoconjugates as ligands. Interactions with its glycan ligands are key to regulating the ability of CD22 to modulate B cell function, the most widely explored of which is antagonizing B cell receptor (BCR) signaling. Most importantly, interactions of CD22 with ligands on the same cell (cis) control the organization of CD22 on the cell surface, which minimizes co-localization with the BCR. In contrast with the modest ability of CD22 to intrinsically dampen BCR signaling, glycan ligands presented on another cell (trans) along with an antigen drawn CD22 and the BCR together within an immunological synapse, strongly inhibiting BCR signaling. New concepts are emerging for how CD22 controls B cell function, such as changes in glycosylation at different stages of B cell differentiation, specifically on GC B cells. Related to these changes, new players, such galectin-9, have been discovered that regulate cell surface nanoclusters of CD22. Roles of glycan ligands in controlling CD22 are the primary focus of this review as we highlight the ability of CD22 to modulate B cell function.

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Section: Beyond Regulation Of the Bcr: Other Roles For Cd22 In Contromentioning

confidence: 53%

Section: Roles Of Glycan Ligands In Controlling Cd22 As a Bcr Inhibitmentioning

confidence: 99%

Coordinated roles for glycans in regulating the inhibitory function of CD22 on B cells

2019

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“…Galectin-4 (Gal-4) is one of the 16 members of the human galectin family, characterized by their participation in a myriad of biological phenomena, with important implications in immunity (Sato et al, 2009 ; Giovannone et al, 2018 ; Martínez Allo et al, 2018 ), inflammation, and cancer (Elola et al, 2018 ). They exert their functions through their ability to bind β-galactoside-containing glycans, toward which the different galectins present different affinities and selectivities.…”

Section: Introductionmentioning

confidence: 99%

Galectin-4 N-Terminal Domain: Binding Preferences Toward A and B Antigens With Different Peripheral Core Presentations

et al. 2021

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The tandem-repeat Galectin-4 (Gal-4) contains two different domains covalently linked through a short flexible peptide. Both domains have been shown to bind preferentially to A and B histo blood group antigens with different affinities, although the binding details are not yet available. The biological relevance of these associations is unknown, although it could be related to its attributed role in pathogen recognition. The presentation of A and B histo blood group antigens in terms of peripheral core structures differs among tissues and from that of the antigen-mimicking structures produced by pathogens. Herein, the binding of the N-terminal domain of Gal-4 toward a group of differently presented A and B oligosaccharide antigens in solution has been studied through a combination of NMR, isothermal titration calorimetry (ITC), and molecular modeling. The data presented in this paper allow the identification of the specific effects that subtle chemical modifications within this antigenic family have in the binding to the N-terminal domain of Gal-4 in terms of affinity and intermolecular interactions, providing a structural-based rationale for the observed trend in the binding preferences.

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“…Antibodies to disialylated GSLs can neutralize shed gangliosides and thus help to restore the diminished T and B cell functions, caused by GSLs. However, as only a few antigens have been identified by TIL-B cells (43–46) our TIL-B disialylated ganglioside binder antibody fragments could be a real asset. Based on the results, we can conclude that TIL-B cells‘ immunoglobulin variable region gene usage with unique disialylated glycosphingolipid revealing capacity is a subject to be harnessed by further antibody engineering, in order to develop cancer targeting tools.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Associated Disialylated Glycosphingolipid Antigen-Revealing Antibodies Found in Melanoma Patients' Immunoglobulin Repertoire Suggest a Two-Direction Regulation Mechanism Between Immune B Cells and the Tumor

et al. 2019

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There is far less information available about the tumor infiltrating B (TIL-B) cells, than about the tumor infiltrating T cells. We focused on discovering the features and potential role of B lymphocytes in solid tumors. Our project aimed to develop innovative strategies to define cancer membrane structures. We chose two solid tumor types, with variable to considerable B cell infiltration. The strategy we set up with invasive breast carcinoma, showing medullary features, has been introduced and standardized in metastatic melanoma. After detecting B lymphocytes by immunohistochemistry, VH-JH, Vκ-Jκ immunoglobulin rearranged V region genes were amplified by RT-PCR, from TIL-B cDNA. Immunoglobulin variable-region genes of interest were cloned, sequenced, and subjected to a comparative DNA analysis. Single-chain variable (scFv) antibody construction was performed in selected cases to generate a scFv library and to test tumor binding capacity. DNA sequence analysis revealed an overrepresented VH3-1 cluster, represented both in the breast cancer and the melanoma TIL-B immunoglobulin repertoire. We observed that our previously defined anti GD3 ganglioside-binder antibody-variable region genes were present in melanoma as well. Our antibody fragments showed binding potential to disialylated glycosphingolipids (GD3 ganglioside) and their O acetylated forms on melanoma cancer cells. We conclude that our results have a considerable tumor immunological impact, as they reveal the power of TIL-B cells to recognize strong tumor-associated glycosphingolipid structures on melanomas and other solid tumors. As tumor-derived gangliosides affect immune cell functions and reduce the B lymphocytes' antibody production, we suspect an important B lymphocyte and cancer cell crosstalk mechanism. We not only described the isolation and specificity testing of the tumor infiltrating B cells, but also showed the TIL-B cells' highly tumor-associated GD3 ganglioside-revealing potential in melanomas. The present data help to identify new cancer-associated biomarkers that may serve for novel cancer diagnostics. The two-direction regulation mechanism between immune B cells and the tumor could eventually be developed into an innovative cancer treatment strategy.

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Galectin-Glycan Interactions as Regulators of B Cell Immunity

Cited by 42 publications

References 74 publications

Coordinated roles for glycans in regulating the inhibitory function of CD22 on B cells

Coordinated roles for glycans in regulating the inhibitory function of CD22 on B cells

Galectin-4 N-Terminal Domain: Binding Preferences Toward A and B Antigens With Different Peripheral Core Presentations

Tumor-Associated Disialylated Glycosphingolipid Antigen-Revealing Antibodies Found in Melanoma Patients' Immunoglobulin Repertoire Suggest a Two-Direction Regulation Mechanism Between Immune B Cells and the Tumor

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