Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance

Minguet, Susana; Kläsener, Kathrin; Schaffer, Anna-Maria; Fiala, Gina J.; Osteso-Ibáñez, Teresa; Raute, Katrin; Navarro-Lérida, Inmaculada; Hartl, Frederike A.; Seidl, Maximilian; Reth, Michael; Pozo, Miguel Á. del

doi:10.1038/ni.3813

Cited by 40 publications

(62 citation statements)

References 52 publications

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“…These IgM and IgD type BCRs possess identical antigen‐binding sites, but differ in their membrane‐bound heavy chain isoforms. GM1‐enriched membrane lipid rafts involved in BCR signaling may be responsible for the ganglioside‐related immune functions of B lymphocytes . IgM‐BCR is not closely localized to GM1‐enriched lipid rafts in resting B cells, whereas IgD‐BCR is located adjacent to these lipid domains .…”

Section: Gangliosides In Adaptive Immunitymentioning

confidence: 99%

“…IgM‐BCR is not closely localized to GM1‐enriched lipid rafts in resting B cells, whereas IgD‐BCR is located adjacent to these lipid domains . BCR stimulation induces the translocation of IgM‐BCRs into GM1‐enriched lipid rafts in a caveolin‐1‐dependent manner, whereas IgD‐BCRs are excluded from these lipid domains , resulting in the clustering of IgM‐ and IgD‐BCR nanoclusters. The mechanisms by which IgM and IgD nanoclusters are organized in GM1‐enriched lipid rafts and modulate BCR signaling remain unknown.…”

Section: Gangliosides In Adaptive Immunitymentioning

confidence: 99%

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The regulatory roles of glycosphingolipid‐enriched lipid rafts in immune systems

et al. 2018

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Lipid rafts formed by glycosphingolipids (GSLs) on cellular membranes play important roles in innate and adaptive immunity. Lactosylceramide (LacCer) forms lipid rafts on plasma and granular membranes of human neutrophils. These LacCer‐enriched lipid rafts bind directly to pathogenic components, such as pathogenic fungi‐derived β‐glucan and Mycobacteria‐derived lipoarabinomannan via carbohydrate‐carbohydrate interactions, and mediate innate immune responses to these pathogens. In contrast, a‐series and o‐series gangliosides form distinct rafts on CD4+ and CD8+ T cell subsets, respectively, contributing to the respective functions of these cells and stimulating adaptive immune responses through T cell receptors. These findings suggest that gangliosides play indispensable roles in T cell selection and activation. This Review introduces the involvement of GSL‐enriched lipid rafts in innate and adaptive immunity.

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Section: Gangliosides In Adaptive Immunitymentioning

confidence: 99%

Section: Gangliosides In Adaptive Immunitymentioning

confidence: 99%

The regulatory roles of glycosphingolipid‐enriched lipid rafts in immune systems

et al. 2018

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“…We next examined the role of LAPF in caveolae formation. It has been reported that Cav1 can be phosphorylated by the tyrosine kinase Src and that activated Cav1 promotes caveolae-mediated endocytosis (27,28). On the other hand, Cav2 could not be phosphorylated by Src (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 97%

An endosomal LAPF is required for macrophage endocytosis and elimination of bacteria

Qin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Macrophages can internalize the invading pathogens by raft/caveolae and/or clathrin-dependent endocytosis and elicit an immune response against infection. However, the molecular mechanism for macrophage endocytosis remains elusive. Here we report that LAPF (lysosome-associated and apoptosis-inducing protein containing PH and FYVE domains) is required for caveolae-mediated endocytosis.Lapf-deficient macrophages have impaired capacity to endocytose and eliminate bacteria. Macrophage-specificLapf-deficient mice are more susceptible toEscherichia coli(E. coli) infection with higher bacterial loads. Moreover,Lapfdeficiency impairs TLR4 endocytosis, resulting in attenuated production of TLR-triggered proinflammatory cytokines. LAPF is localized to early endosomes and interacts with caveolin-1. Phosphorylation of LAPF by the tyrosine kinase Src is required for LAPF-Src-Caveolin complex formation and endocytosis and elimination of bacteria. Collectively, our work demonstrates that LAPF is critical for endocytosis of bacteria and induction of inflammatory responses, suggesting that LAPF and Src could be potential targets for the control of infectious diseases.

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“…Additionally, different subsets of leukocytes derived from CAV1-null mice have been analyzed in terms of response to either parasitic [ 46 ] or bacterial infection [ 27 ]. Also, the ability of lymphocytes from CAV1-null mice to induce a humoral [ 47 ] or cytotoxic immune response [ 48 ] has been reported. However, studies have not focused on systemic inflammation in the absence of immune triggers.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1-Knockout Mouse as a Model of Inflammatory Diseases

Codrici

Albulescu

Popescu

et al. 2018

Journal of Immunology Research

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Caveolin-1 (CAV1) is the scaffold protein of caveolae, which are minute invaginations of the cell membrane that are involved in endocytosis, cell signaling, and endothelial-mediated inflammation. CAV1 has also been reported to have a dual role as either a tumor suppressor or tumor promoter, depending on the type of cancer. Inflammation is an important player in tumor progression, but the role of caveolin-1 in generating an inflammatory milieu remains poorly characterized. We used a caveolin-1-knockout (CAV1−/−) mouse model to assess the inflammatory status via the quantification of the pro- and anti-inflammatory cytokine levels, as well as the ability of circulating lymphocytes to respond to nonspecific stimuli by producing cytokines. Here, we report that the CAV1−/− mice were characterized by a low-grade systemic proinflammatory status, with a moderate increase in the IL-6, TNF-α, and IL-12p70 levels. CAV1−/− circulating lymphocytes were more prone to cytokine production upon nonspecific stimulation than the wild-type lymphocytes. These results show that CAV1 involvement in cell homeostasis is more complex than previously revealed, as it plays a role in the inflammatory process. These findings indicate that the CAV1−/− mouse model could prove to be a useful tool for inflammation-related studies.

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Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance

Cited by 40 publications

References 52 publications

The regulatory roles of glycosphingolipid‐enriched lipid rafts in immune systems

The regulatory roles of glycosphingolipid‐enriched lipid rafts in immune systems

An endosomal LAPF is required for macrophage endocytosis and elimination of bacteria

Caveolin-1-Knockout Mouse as a Model of Inflammatory Diseases

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