B cell receptor-induced protein dynamics and the emerging role of SUMOylation revealed by proximity proteomics

Awoniyi, Luqman O; Cunha, Diogo M; Sarapulov, Alexey V; Hernández-Pérez, Sara; Runsala, Marika; Tejeda-González, Blanca; Šuštar, Vid; Balci, M Özge; Petrov, Petar; Mattila, Pieta K.

doi:10.1242/jcs.261119

Cited by 3 publications

(2 citation statements)

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“…We expect that proteomics could be key in the quest to unravel important new insights into lysosome functions upon B cell activation. Analysis of isolated lysosomes, like in macrophages (Gao et al, 2017), or modern proteomics tools like LysoIP (Laqtom, 2023) and proximity proteomics (similar to Awoniyi et al [2023]), combined, for example, with the information of the overall proteome recruited to the IS upon B cell activation (Cunha et al, 2023aPreprint, 2023b hold great promise for new insights of the lysosomal heterogeneity and LRO functions. Understanding B cell activation at the molecular level would help us to decipher the pathogenesis of various autoimmune conditions or B cell lymphomas and has implications on immunotherapeutic aspects as well.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

“…As the function of immune cells is to be sensitized by pathogenic products, it is not surprising that upon exposure, lysosomes are remodeled in different ways. Various vesicle-linked proteins have been shown to alter their intracellular positioning, for instance, upon BCR engagement (Music et al, 2022;Awoniyi et al, 2023). However, more efforts are required to dissect the functions of the different endosomal players in B cell activation.…”

Section: Hämälistö Et Almentioning

confidence: 99%

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Endolysosomal vesicles at the center of B cell activation

Hämälistö,

Del Valle Batalla,

Yuseff

et al. 2024

Journal of Cell Biology

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The endolysosomal system specializes in degrading cellular components and is crucial to maintaining homeostasis and adapting rapidly to metabolic and environmental cues. Cells of the immune system exploit this network to process antigens or promote cell death by secreting lysosome-related vesicles. In B lymphocytes, lysosomes are harnessed to facilitate the extraction of antigens and to promote their processing into peptides for presentation to T cells, critical steps to mount protective high-affinity antibody responses. Intriguingly, lysosomal vesicles are now considered important signaling units within cells and also display secretory functions by releasing their content to the extracellular space. In this review, we focus on how B cells use pathways involved in the intracellular trafficking, secretion, and function of endolysosomes to promote adaptive immune responses. A basic understanding of such mechanisms poses an interesting frontier for the development of therapeutic strategies in the context of cancer and autoimmune diseases.

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Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Section: Hämälistö Et Almentioning

confidence: 99%

Endolysosomal vesicles at the center of B cell activation

Hämälistö,

Del Valle Batalla,

Yuseff

et al. 2024

Journal of Cell Biology

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2023 Winners: Stephen Coscia, Eirini Tsekitsidou and Rachel Wills

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2024

Journal of Cell Science

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Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor–Proximal Proteins with Immunological Functions

Hoeger,

Drake,

Drake

2024

ImmunoHorizons

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The BCR allows for Ag-driven B cell activation and subsequent Ag endocytosis, processing, and presentation to recruit T cell help. Core drivers of BCR signaling and endocytosis are motifs within the receptor’s cytoplasmic tail (primarily CD79). However, BCR function can be tuned by other proximal cellular elements, such as CD20 and membrane lipid microdomains. To identify additional proteins that could modulate BCR function, we used a proximity-based biotinylation technique paired with mass spectrometry to identify molecular neighbors of the murine IgM BCR. Those neighbors include MHC class II molecules, integrins, various transporters, and membrane microdomain proteins. Class II molecules, some of which are invariant chain–associated nascent class II, are a readily detected BCR neighbor. This finding is consistent with reports of BCR–class II association within intracellular compartments. The BCR is also in close proximity to multiple proteins involved in the formation of membrane microdomains, including CD37, raftlin, and Ig superfamily member 8. Known defects in T cell–dependent humoral immunity in CD37 knockout mice suggest a role for CD37 in BCR function. In line with this notion, CRISPR-based knockout of CD37 expression in a B cell line heightens BCR signaling, slows BCR endocytosis, and tempers formation of peptide–class II complexes. These results indicate that BCR molecular neighbors can impact membrane-mediated BCR functions. Overall, a proximity-based labeling technique allowed for identification of multiple previously unknown BCR molecular neighbors, including the tetraspanin protein CD37, which can modulate BCR function.

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B cell receptor-induced protein dynamics and the emerging role of SUMOylation revealed by proximity proteomics

Cited by 3 publications

References 96 publications

Endolysosomal vesicles at the center of B cell activation

Endolysosomal vesicles at the center of B cell activation

2023 Winners: Stephen Coscia, Eirini Tsekitsidou and Rachel Wills

Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor–Proximal Proteins with Immunological Functions

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