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Cited by 25T-cell and B-cell ImmunologyProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production

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Ushijima, Miho, Uruno, Takehito, Nishikimi, Akihiko, Sanematsu, Fumiyuki, Kamikaseda, Yasuhisa, Kunimura, Kazufumi, Sakata, Daiji, Okada, Takaharu +1 more·2018·Frontiers in Immunology
DOI 10.3389/fimmu.2018.00243PMC PMC5820292
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Abstract

A hallmark of humoral immune responses is the production of antibodies. This process involves a complex cascade of molecular and cellular interactions, including recognition of specific antigen by the B cell receptor (BCR), which triggers activation of B cells and differentiation into plasma cells (PCs). Although activation of the small GTPase Rac has been implicated in BCR-mediated antigen recognition, its precise role in humoral immunity and the upstream regulator remain elusive. DOCK2 is a Rac-specific guanine nucleotide exchange factor predominantly expressed in hematopoietic cells. We found that BCR-mediated Rac activation was almost completely lost in DOCK2-deficient B cells, resulting in defects in B cell spreading over the target cell-membrane and sustained growth of BCR microclusters at the interface. When wild-type B cells were stimulated in vitro with anti-IgM F(ab’)2 antibody in the presence of IL-4 and IL-5, they differentiated efficiently into PCs. However, BCR-mediated PC differentiation was severely impaired in the case of DOCK2-deficient B cells. Similar results were obtained in vivo when DOCK2-deficient B cells expressing a defined BCR specificity were adoptively transferred into mice and challenged with the cognate antigen. In addition, by generating the conditional knockout mice, we found that DOCK2 expression in B-cell lineage is required to mount antigen-specific IgG antibody. Theses results highlight important role of the DOCK2-Rac axis in PC differentiation and IgG antibody responses.

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Cited by

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Authors
Ushijima, M., Uruno, T., Nishikimi, A., Sanematsu, F., Kamikaseda, Y., Kunimura, K., Sakata, D., Okada, T., & Fukui, Y.
Affiliations
  • Kyushu University (JP)
  • Kitasato University (JP)
  • University of Miyazaki (JP)
  • RIKEN Center for Integrative Medical Sciences (JP)
Corresponding author
Uruno, Takehito
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2018-02-16
Volume
9
Pages
243-243
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2018.00243
PMC
PMC5820292
OpenAlex
W2794250903
Cited by
25
References
1
Citations by year
2026: 5 · 2025: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 6 · 2018: 1
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Kyushu University Institutional Repository (QIR) (Kyushu University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Japan Agency for Medical Research and Development
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Society for the Promotion of Science
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
DOCK2, plasma cell differentiation, IgG antibody production, B cell receptor signaling, humoral immunity, conditional knockout mice, adoptive transfer
MeSH terms
Mouse Embryonic Stem Cells, Animals, Cell Differentiation, Cell Membrane, Female, Immunoglobulin G, Lymphocyte Activation, Male, Mice, Inbred C57BL, Plasma Cells, Receptors, Antigen, B-Cell, Transplantation Chimera, Mice, Knockout, Adoptive Transfer, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, rac GTP-Binding Proteins, Models, Animal, Mice, Immunological Synapses, Immunity, Humoral

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