Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding

CD22 functions primarily as a negative regulator of B-cell receptor signaling. The Cd22a allele has been proposed as a candidate allele for murine systemic lupus erythematosus. In this study, we explored the possible expression of aberrant forms of CD22, which differ in the N-terminal sequences constituting the ligand-binding site due to synthesis of abnormally processed Cd22 mRNA, in several Cd22a mouse strains, including C57BL/6 Cd22 congenic mice. The staining pattern of splenic B cells obtained with CY34 anti-CD22 mAb, which was expected to bind poorly to the aberrant CD22, was more heterogeneous in Cd22a mice than in Cd22b mice. Moreover, CD22 detected on B cells of Cd22a mice was expressed more weakly and as a smaller-sized protein, compared with Cd22b mice. Significantly, analysis with a synthetic CD22 ligand demonstrated that Cd22a mice carried a larger proportion of CD22 that was not bound by cis ligands on the B-cell surface than Cd22b mice. Finally, the study of C57BL/6 Cd22 congenic mice revealed that Cd22a B cells displayed a phenotype reminiscent of constitutively activated B cells (reduced surface IgM expression and augmented MHC class II expression), as reported for B cells expressing a mutant CD22 lacking the ligand-binding domain. Our demonstration that Cd22a B cells express aberrant forms of CD22, which can potentially deregulate B-cell signaling because of their decreased ligand-binding capacity, provides further support for Cd22a as a potential candidate allele for murine systemic lupus erythematosu

BPW34 Commercial p-i-n Diodes for High-level 1-MeV Neutron Equivalent Fluence Monitoring

International audienc

Forêt équatoriale et savanes congolaises / par M. le commandant Moll,...

Avec mode text

Endoscopic necrosectomy using electric conductivity: anchoring the snare tip into a groove made with Endocut may improve necrosis grasping

International audienc

Differentially regulated expression and function of CD22 in activated B-1 and B-2 lymphocytes

CD22 is a B cell-restricted transmembrane protein that apparently controls signal transduction thresholds initiated through the B cell Ag receptor (BCR) in response to Ag. However, it is still poorly understood how the expression of CD22 is regulated in B cells after their activation. Here we show that the expression levels of CD22 in conventional B-2 cells are markedly down-regulated after cross-linking of BCR with anti-IgM mAb but are up-regulated after stimulation with LPS, anti-CD40 mAb, or IL-4. In contrast, treatment with anti-IgM mAb barely modulated the expression levels of CD22 in CD5(+) B-1 cells, consistent with a weak Ca(2+) response in anti-IgM-treated CD5(+) B-1 cells. Moreover, in CD22-deficient mice, anti-IgM treatment did not trigger enhanced Ca(2+) influx in CD5(+) B-1 cells, unlike CD22-deficient splenic B-2 cells, suggesting a relatively limited role of CD22 in BCR signaling in B-1 cells. In contrast, CD22 levels were markedly down-regulated on wild-type B-1 cells in response to LPS or unmethylated CpG-containing oligodeoxynucleotides. These data indicate that the expression and function of CD22 are differentially regulated in B-1 and conventional B-2 cells, which are apparently implicated in innate and adaptive immunity, respectively

AlN coatings of 3D titanium alloy structures elaborated by Electron Beam Melting

International audienc

Differential control of CD22 ligand expression on B and T lymphocytes, and enhanced expression in murine systemic lupus

OBJECTIVE: CD22, a B cell-restricted transmembrane glycoprotein, regulates B cell antigen receptor signaling upon interaction with alpha2,6-linked sialic acid-bearing glycans, which act as ligands and are expressed on B and T cells. In this study, we investigated how the expression of CD22 ligand (CD22L) is modulated following lymphocyte activation or during the course of systemic lupus erythematosus (SLE). METHODS: The expression levels of CD22L on B and T cells in nonautoimmune mice were assessed by flow cytometric analysis using a soluble recombinant form of CD22, following stimulation with antigen or mitogen in vitro. In addition, the expression levels of CD22L on circulating lymphocytes were correlated with the progression of SLE in lupus-prone mice. RESULTS: We observed a constitutive expression of CD22L on mature B cells, but not T cells, in nonautoimmune mice. However, CD22L levels were up-regulated selectively on T cells (but not B cells) stimulated with antigens in vitro, while their expression levels on B cells was up-modulated following polyclonal activation with lipopolysaccharide. Furthermore, expression of CD22L was increased on circulating B cells (and to a lesser extent on T cells) in parallel with progression of SLE in several different lupus-prone mice and in a cohort of (C57BL/6 x [NZB x C57BL/6.Yaa]F(1)) backcross mice. CONCLUSION: The expression of CD22L is differentially regulated in B and T cells, and high expression of CD22L on circulating B cells is a marker for development of severe SLE, suggesting a role for CD22-CD22L interactions in SLE as well as in the regulation of humoral immunity