%0 Journal Article %1 meyerCullinCrucialProB2020 %A Meyer, Sarah J. %A Böser, Alexander %A Korn, Marina A. %A Koller, Claudia %A Bertocci, Barbara %A Reimann, Lena %A Warscheid, Bettina %A Nitschke, Lars %C United States %D 2020 %J Journal of immunology (Baltimore, Md. : 1950) %K 2/*immunology,to_read,Ubiquitin-Protein Acid Activation/immunology,Mice,Mice Animals,Apoptosis/immunology,B-Lymphocytes/*immunology,Bone Antigen B-Cell/immunology,Sialic B-Lymphoid/*immunology,Receptors Binding C57BL,Precursor Cells Ig-like Inbred Lectin Ligases/immunology Line,Cell Marrow/immunology,Cell Proliferation/*physiology,Cullin Proteins/*immunology,Lymphocyte %N 12 %P 3360--3374 %R 10.4049/jimmunol.1900925 %T Cullin 3 Is Crucial for Pro-B Cell Proliferation, Interacts with CD22, and Controls CD22 Internalization on B Cells. %V 204 %X 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.

@article{meyerCullinCrucialProB2020, 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.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {United States}, author = {Meyer, Sarah J. and B{\"o}ser, Alexander and Korn, Marina A. and Koller, Claudia and Bertocci, Barbara and Reimann, Lena and Warscheid, Bettina and Nitschke, Lars}, biburl = {https://www.bibsonomy.org/bibtex/268bf9e0a85903d3e94ad65b05d9e7e21/warscheidlab}, copyright = {Copyright {\copyright} 2020 by The American Association of Immunologists, Inc.}, doi = {10.4049/jimmunol.1900925}, interhash = {1ec12093552ccd399d76909711f7713d}, intrahash = {68bf9e0a85903d3e94ad65b05d9e7e21}, issn = {1550-6606 0022-1767}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, keywords = {2/*immunology,to_read,Ubiquitin-Protein Acid Activation/immunology,Mice,Mice Animals,Apoptosis/immunology,B-Lymphocytes/*immunology,Bone Antigen B-Cell/immunology,Sialic B-Lymphoid/*immunology,Receptors Binding C57BL,Precursor Cells Ig-like Inbred Lectin Ligases/immunology Line,Cell Marrow/immunology,Cell Proliferation/*physiology,Cullin Proteins/*immunology,Lymphocyte}, langid = {english}, month = jun, number = 12, pages = {3360--3374}, pmid = {32341059}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {Cullin 3 {{Is Crucial}} for {{Pro-B Cell Proliferation}}, {{Interacts}} with {{CD22}}, and {{Controls CD22 Internalization}} on {{B Cells}}.}, volume = 204, year = 2020 }