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.
%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
}