Cullin 3 Is Crucial for Pro-B Cell Proliferation, Interacts with CD22, and Controls CD22 Internalization on B Cells

Meyer SJ, Böser A, Korn M, Koller C, Bertocci B, Reimann L, Warscheid B, Nitschke L (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 204

Pages Range: 3360-3374

Journal Issue: 12

DOI: 10.4049/jimmunol.1900925

Abstract

B lymphocytes are important players of the adaptive immune system. However, not just activation of B cells but also regulation of B cell signaling is important to prevent hyperactivity and dysregulation of the immune response. Different mechanisms and proteins contribute to this balance. One of these is CD22, a member of the Siglec family. It is an inhibitory coreceptor of the BCR and inhibits B cell activation. Upon BCR stimulation, CD22-dependent inhibition of BCR signaling results in a decreased calcium mobilization. Although some CD22 binding partners have already been identified, the knowledge about the CD22 interactome is still incomplete. In this study, quantitative affinity purification-mass spectrometry enabled the delineation of the CD22 interactome in the B cell line DT40. These data will clarify molecular mechanisms and CD22 signaling events after BCR activation and revealed several new CD22-associated proteins. One new identified interaction partner is the E3 ubiquitin ligase cullin 3, which was revealed to regulate CD22 surface expression and clathrin-dependent CD22 internalization after BCR stimulation. Furthermore cullin 3 was identified to be important for B lymphocytes in general. B cell-specific cullin 3-deficient mice show reduced developing B cells in the bone marrow and a severe pro-B cell proliferation defect. Mature B cells in the periphery are also reduced and characterized by increased CD22 expression and additionally by preactivated and apoptotic phenotypes. The findings reveal novel functions of cullin 3 in B lymphocytes, namely regulating CD22 surface expression and internalization after B cell activation, as well as promoting proliferation of pro-B cells.

Authors with CRIS profile

Involved external institutions

Albert-Ludwigs-Universität Freiburg Germany (DE) University of Paris 5 - René Descartes / Université Paris V René Descartes France (FR)

How to cite

APA:

Meyer, S.J., Böser, A., Korn, M., Koller, C., Bertocci, B., Reimann, L.,... Nitschke, L. (2020). Cullin 3 Is Crucial for Pro-B Cell Proliferation, Interacts with CD22, and Controls CD22 Internalization on B Cells. Journal of Immunology, 204(12), 3360-3374. https://doi.org/10.4049/jimmunol.1900925

MLA:

Meyer, Sarah Johanna, et al. "Cullin 3 Is Crucial for Pro-B Cell Proliferation, Interacts with CD22, and Controls CD22 Internalization on B Cells." Journal of Immunology 204.12 (2020): 3360-3374.

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