CD81 on B cells promotes interleukin 4 secretion and antibody production during T helper type 2 immune responses

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123

117

CD81 is a widely expressed tetraspanin that associates in B cells with CD19 in the CD19-CD21-CD81 signaling complex. CD81 is necessary for normal CD19 expression; cd81−/− B cells express lower levels of CD19, especially cd81−/− small pre-BII cells, which are almost devoid of surface CD19. The dependence of CD19 expression on CD81 is specific to this particular tetraspanin since cd9−/− B cells express normal levels of CD19. Furthermore, expression of human CD81 in mouse cd81−/− B cells restored surface CD19 to normal levels. Quantitative analysis of CD19 mRNA demonstrated normal levels, even in cd81−/− pre-BII cells. Analysis of CD19 at the protein level identified two CD19 glycoforms in both wild-type and cd81−/− B cells. The higher Mr glycoform is significantly reduced in cd81−/− B cells and is endoglycosidase H (endo-H) resistant. In contrast, the low Mr glycoform is comparably expressed in cd81−/− and in wild-type B cells and is endo-H sensitive. Because endo-H sensitivity is tightly correlated with endoplasmic reticulum localization, we suggest that the dependency of CD19 expression on CD81 occurs in a postendoplasmic reticulum compartment where CD81 is necessary for normal trafficking or for surface membrane stability of CD19.

mentioning

confidence: 89%

The Tetraspanin CD81 Regulates the Expression of CD19 During B Cell Development in a Postendoplasmic Reticulum Compartment

Shoham

Rajapaksa

Boucheix

et al. 2003

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123

117

“…Although CD81-deficient mice exhibit normal maturation of all lymphoid cells, they show a decreased Ab production in response to protein Ags (12,13). Hence, chimeric mice in which only B cells lacked CD81 have reduced Ab production upon exposure to a Th2 stimulus (14). Lately, it has been reported that CD81…”

mentioning

confidence: 99%

Cutting Edge: Dynamic Redistribution of Tetraspanin CD81 at the Central Zone of the Immune Synapse in Both T Lymphocytes and APC

Mittelbrunn

Yáñez-Mó

Sancho

et al. 2002

129

104

The tetraspanin CD81 has been involved in T-dependent B cell-mediated immune responses. However, the behavior of CD81 during immune synapse (IS) formation has not been elucidated. We determined herein that CD81 redistributed to the contact area of T cell-B cell and T cell-dendritic cell conjugates in an Ag-dependent manner. Confocal microscopy showed that CD81 colocalized with CD3 at the central supramolecular activation complex. Videomicroscopy studies with APC or T cells transiently expressing CD81-green fluorescent protein (GFP) revealed that in both cells CD81 redistributed toward the central supramolecular activation complex. In T lymphocytes, CD81-GFP rapidly redistributed to the IS, whereas, in the APC, CD81-GFP formed a large accumulation in the contact area that later concentrated in a discrete cluster and waves of CD81 accumulated at the IS periphery. These results suggest a relevant role for CD81 in the topography of the IS that would explain its functional implication in T cell-B cell collaboration.

“…In this regard, several studies have emphasized the role of the tetraspanin CD81 in promoting a potent costimulatory signal to T cells (6) and in controlling sustained T cell signaling and molecular organization of the immune synapse (7). Additionally, whereas lymphoid development in CD81 2/2 mice is normal (8)(9)(10), T cells from CD81 2/2 mice present a hyperproliferative phenotype after anti-CD3 stimulation and impaired development of Th2 responses (8,11).…”

mentioning

confidence: 99%

CD81 Controls Immunity to Listeria Infection through Rac-Dependent Inhibition of Proinflammatory Mediator Release and Activation of Cytotoxic T Cells

Hoyo

Ramírez-Huesca

Levy

et al. 2015

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Despite recent evidence on the involvement of CD81 in pathogen binding and Ag presentation by dendritic cells (DCs), the molecular mechanism of how CD81 regulates immunity during infection remains to be elucidated. To investigate the role of CD81 in the regulation of defense mechanisms against microbial infections, we have used the Listeria monocytogenes infection model to explore the impact of CD81 deficiency in the innate and adaptive immune response against this pathogenic bacteria. We show that CD81−/− mice are less susceptible than wild-type mice to systemic Listeria infection, which correlates with increased numbers of inflammatory monocytes and DCs in CD81−/− spleens, the main subsets controlling early bacterial burden. Additionally, our data reveal that CD81 inhibits Rac/STAT-1 activation, leading to a negative regulation of the production of TNF-α and NO by inflammatory DCs and the activation of cytotoxic T cells by splenic CD8α+ DCs. In conclusion, this study demonstrates that CD81–Rac interaction exerts an important regulatory role on the innate and adaptive immunity against bacterial infection and suggests a role for CD81 in the development of novel therapeutic targets during infectious diseases.