The rac activator DOCK2 mediates plasma cell differentiation and IgG antibody production

Miho Ushijima, Takehito Uruno, Akihiko Nishikimi, Fumiyuki Sanematsu, Yasuhisa Kamikaseda, Kazufumi Kunimura, Daiji Sakata, Takaharu Okada, Yoshinori Fukui

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. These results highlight important role of the DOCK2-Rac axis in PC differentiation and IgG antibody responses.

Original languageEnglish
Article number243
JournalFrontiers in Immunology
Volume9
Issue numberFEB
DOIs
Publication statusPublished - Feb 16 2018

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Plasma Cells
Antibody Formation
Cell Differentiation
B-Lymphocytes
Immunoglobulin G
B-Cell Antigen Receptors
Humoral Immunity
Guanine Nucleotide Exchange Factors
Antigens
Monomeric GTP-Binding Proteins
Antibodies
Interleukin-5
Cell Lineage
Knockout Mice
Interleukin-4
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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The rac activator DOCK2 mediates plasma cell differentiation and IgG antibody production. / Ushijima, Miho; Uruno, Takehito; Nishikimi, Akihiko; Sanematsu, Fumiyuki; Kamikaseda, Yasuhisa; Kunimura, Kazufumi; Sakata, Daiji; Okada, Takaharu; Fukui, Yoshinori.

In: Frontiers in Immunology, Vol. 9, No. FEB, 243, 16.02.2018.

Research output: Contribution to journalArticle

Ushijima, Miho ; Uruno, Takehito ; Nishikimi, Akihiko ; Sanematsu, Fumiyuki ; Kamikaseda, Yasuhisa ; Kunimura, Kazufumi ; Sakata, Daiji ; Okada, Takaharu ; Fukui, Yoshinori. / The rac activator DOCK2 mediates plasma cell differentiation and IgG antibody production. In: Frontiers in Immunology. 2018 ; Vol. 9, No. FEB.
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