Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling

Collins, Brian E.; Smith, Brian A.; Bengtson, Per; Paulson, James C.

doi:10.1038/ni1283

Cited by 139 publications

(166 citation statements)

References 54 publications

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“…In addition, mice with a loss of a2,6Sia on the surface by deficiency of the enzyme ST6GalI have reduced Ca 2+ signaling on conventional B2 cells. St6galI 2/2 Cd22 2/2 mice revealed that CD22 on conventional B cells is responsible for this (12,13). St6galI 2/2 mice had a higher association of CD22 with the BCR.…”

Section: Discussionmentioning

confidence: 95%

“…The binding to a2,6Sia on neighboring CD22 molecules on the B cell surface prevents the CD22 association to the BCR and thereby affects the strength of inhibition (12)(13)(14). Because the Siglec-G inhibitory protein is expressed throughout the B cell lineage and in all subpopulations of B cells, it is unclear why it shows a B1 cellrestricted inhibitory effect.…”

Section: The Journal Of Immunologymentioning

confidence: 99%

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The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells

Hutzler

Özgör

Naito-Matsui

et al. 2014

The Journal of Immunology

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Siglec-G is an inhibitory receptor on B1 cells. Siglec-G–deficient mice show a large B1 cell expansion, owing to higher BCR-induced Ca2+ signaling and enhanced cellular survival. It was unknown why Siglec-G shows a B1 cell–restricted inhibitory function. With a new mAb we could show a comparable Siglec-G expression on B1 cells and conventional B2 cells. However, Siglec-G has a different ligand sialic acid–binding pattern on peritoneal B1 cells than on splenic B cells, and its sialic acid ligands are expressed differentially on these two B cell populations, suggesting that cis-ligand binding plays a crucial role on B1 cells. This observation was further studied by generation of Siglec-G knockin mice with a mutated ligand-binding domain. These mice show increased B1 cell numbers, increased B1 cell Ca2+ signaling, better B1 cell survival, and changes in the B1 cell Ig repertoire. These phenotypes are very similar to Siglec-G–deficient mice. The mutation of the ligand-binding domain of Siglec-G strongly reduces the Siglec-G–IgM association on the B cell surface. Thus, Siglec-G sialic acid–dependent binding to the BCR is crucial for the B1 cell–restricted inhibitory function of Siglec-G and is regulated in an opposite way to that of the related protein CD22 (Siglec-2) on B cells.

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Section: Discussionmentioning

confidence: 95%

Section: The Journal Of Immunologymentioning

confidence: 99%

The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells

Hutzler

Özgör

Naito-Matsui

et al. 2014

The Journal of Immunology

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“…CD22 interacts with glycoprotein ligands on the same cell, in cis, and on adjacent cells, in trans. Interaction of CD22 with B cell ligands in cis has been suggested to modulate the activity of CD22 as a negative regulator of B cell signaling (23,25,56,57). However, CD22 was initially described as a T cell adhesion protein and has been demonstrated to interact with trans ligands on adjacent cells (23,58,59).…”

Section: Discussionmentioning

confidence: 99%

Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling ofN-Linked Glycans

Comelli¹,

Sutton-Smith

Qi³

et al. 2006

The Journal of Immunology

110

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Differentiation and activation of lymphocytes are documented to result in changes in glycosylation associated with biologically important consequences. In this report, we have systematically examined global changes in N-linked glycosylation following activation of murine CD4 T cells, CD8 T cells, and B cells by MALDI-TOF mass spectrometry profiling, and investigated the molecular basis for those changes by assessing alterations in the expression of glycan transferase genes. Surprisingly, the major change observed in activated CD4 and CD8 T cells was a dramatic reduction of sialylated biantennary N-glycans carrying the terminal NeuGcα2-6Gal sequence, and a corresponding increase in glycans carrying the Galα1-3Gal sequence. This change was accounted for by a decrease in the expression of the sialyltransferase ST6Gal I, and an increase in the expression of the galactosyltransferase, α1-3GalT. Conversely, in B cells no change in terminal sialylation of N-linked glycans was evident, and the expression of the same two glycosyltransferases was increased and decreased, respectively. The results have implications for differential recognition of activated and unactivated T cells by dendritic cells and B cells expressing glycan-binding proteins that recognize terminal sequences of N-linked glycans.

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“…The diffusion of CD22 is primarily regulated by interactions of its lectin domain with cell surface glycoproteins, including PTPRC. Mutation of the lectin binding domain increases CD22 diffusion and improves the negative regulation of BCR signaling [108][109][110] .…”

Section: [H1] Cytoskeletal Regulation Of Bcr Signallingmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

118

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The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton couples extensively to B cell receptor (BCR) signalling pathways and its defects can either enhance or suppress B cell activation. Recent insights from single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion, and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also play a role in the adaptation of B cell subsets to specialized tasks during antibody responses.3

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Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling

Cited by 139 publications

References 54 publications

The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells

The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells

Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling ofN-Linked Glycans

Cytoskeletal control of B cell responses to antigens

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