Plasma membrane topography governs the 3D dynamic localization of IgM B cell antigen receptor clusters

Saltukoglu, Deniz; Özdemir, Buğra; Holtmannspötter, Michael; Reski, Ralf; Piehler, Jacob; Kurre, Rainer; Reth, Michael

doi:10.15252/embj.2022112030

Cited by 17 publications

(15 citation statements)

References 86 publications

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“…We previously have shown that different classes of the BCR are localized together with other surface proteins inside class-specific protein nanodomains and at distinct topographic locations (24, 25). To test whether or not the IgM-BCR or IgG1-BCR Ramos B cells differ in the expression of other B cell surface proteins we stained these cells with antibodies directed against 29 different B cell surface markers.…”

Section: Resultsmentioning

confidence: 99%

Class-specific sensing of HIV-1 antigens by the B cell antigen receptor depends on the CH1 domain

Ortiz,

Anasti,

Pane

et al. 2023

Preprint

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SUMMARYHow different classes of the B cell antigen receptor (BCR) sense viral antigens used in vaccination protocols is poorly understood. Here we study antigen binding and sensing of Ramos B cells expressing BCRs of either the IgM or IgG1 class with a specificity for the CD4-binding-site of the envelope (Env) protein of the human immune deficiency virus-1 (HIV-1). We find that, in spite of their identical antigen binding site, the two BCR classes differ drastically from each other in that the IgM-BCR and IgG1-BCR bind preferentially to monovalent and polyvalent antigens, respectively. By generating an IgM/IgG1 chimeric BCR we found that the class-specific antigen-sensing behavior can be transferred with the CH1γ domain from the IgG1-BCR to the IgM-BCR. Our results indicate that the class-switching process not only results in the production of antibody classes with different effector functions but also alters the antigen sensing of secondary B lymphocytes. These findings suggest that antigen valency in existing vaccination protocols should be modified and altered between primary versus secondary (booster) immunization.

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Section: Resultsmentioning

confidence: 99%

Class-specific sensing of HIV-1 antigens by the B cell antigen receptor depends on the CH1 domain

Ortiz,

Anasti,

Pane

et al. 2023

Preprint

Self Cite

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“…30 For example, B cell receptors (BCRs) are also clustered. 31 In the periphery pre-secreted natural antibodies could compete with them for reaction with antigens. More antigen would be required to produce a given effect.…”

Section: Selectionmentioning

confidence: 99%

“…Thus, the antigen dose‐response requirements for these anatomically separate processes, while perhaps having fundament similarities, would likely cover different ranges 30 . For example, B cell receptors (BCRs) are also clustered 31 . In the periphery pre‐secreted natural antibodies could compete with them for reaction with antigens.…”

Section: Positive Repertoire Selectionmentioning

confidence: 99%

Aggregation‐prone peptides from within a non‐self‐protein homoaggregate are preferred for MHC association: Historical overview

Forsdyke

2023

Scand J Immunol

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New technologies assist re‐evaluation of hypotheses on generation of immune cell repertoires and distinctions of self from non‐self. Findings include positive correlations between peptide propensities to aggregate and their binding to major histocompatibility complex (MHC) proteins. This recalls the hypothesis that foreign proteins may homoaggregate in host cytosols prior to releasing their peptides (p) to form pMHC complexes. Clues to this included aggregation‐related phenomena associated with infections (rouleaux formation, pyrexia, certain brain diseases). By virtue of ‘promiscuous’ gene expression by thymic presenting cells – perhaps adapted from earlier evolving gonadal mechanisms – developing T cells monitor surface pMHC clusterings. This evaluates intracellular concentrations of the corresponding proteins, and hence, following Burnet's two signal principle, degrees of self‐reactivity. After positive selection in the thymic cortex for reactivity with ‘near‐self’, high‐level pMHC clustering suffices in the medulla for negatively selection. Following Burnet's principle, in the periphery low‐level clustering suffices for T cell stimulation and high‐level clustering again provokes negative selection (immunological tolerance). For evolving intracellular pathogens, fine‐tuned polymorphisms of their host species have limited to ‘near‐self’ some mimicking adaptations. It is proposed that while entire pathogen proteins may have evolved to minimize their aggregability, the greater aggregability of their peptides remains partially hidden within. Two‐step proofreading mechanisms in prospective hosts select proteins containing aggregable peptide for the generation of pMHC clusters at the surface of presenting cells. Through mutations, some proteins of pathogens and cancer cells tend to converge towards the host ‘near‐self’ that its T cells have auditioned to address.

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“…6 Similar role of microvilli was described or predicted for other immune cells. [7][8][9] Nanotechnology introduced a variety of objects with feasible sizes and functional advantages to mimic the geometry of microvilli. 10 Nanoparticles are broadly available in a variety of compositions, sizes and surface functionalization.…”

Section: Introductionmentioning

confidence: 99%

Cell surface morphology mimicking nano-bio platform for immune cell stimulation

Varghese,

González-Navarro,

Guerra

et al. 2024

Preprint

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Studying the complex realm of cellular communication and interactions by fluorescence microscopy requires sample fixation on a transparent substrate. To activate T cells, which are pivotal in controlling the immune system, it is important to present the activating antigen in a spatial arrangement similar to the nature of the antigen-presenting cell, including the presence of ligands on microvilli. Similar arrangement is predicted for some other immune cells. In this work, immune cell-stimulating platform based on nanoparticle-ligand conjugates have been developed using a scalable, affordable, and broadly applicable technology, which can be readily deployed without the need for state-of-the-art nanofabrication instruments. The validation of surface biofunctionalization was performed by combination of fluorescence and atomic force microscopy techniques. We demonstrate that the targeted system serves as a biomimetic scaffold on which immune cells make primary contact with the microvilli-mimicking substrate and exhibit stimulus-specific activation.

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Plasma membrane topography governs the 3D dynamic localization of IgM B cell antigen receptor clusters

Cited by 17 publications

References 86 publications

Class-specific sensing of HIV-1 antigens by the B cell antigen receptor depends on the CH1 domain

Class-specific sensing of HIV-1 antigens by the B cell antigen receptor depends on the CH1 domain

Aggregation‐prone peptides from within a non‐self‐protein homoaggregate are preferred for MHC association: Historical overview

Cell surface morphology mimicking nano-bio platform for immune cell stimulation

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