CD27/CD70 Interaction Augments IgE Secretion by Promoting the Differentiation of Memory B Cells into Plasma Cells

Author:

Nagumo Haruo1,Agematsu Kazunaga1,Shinozaki Koji1,Hokibara Sho1,Ito Susumu2,Takamoto Masaya3,Nikaido Toshio4,Yasui Kozo1,Uehara Yoshio5,Yachie Akihiro6,Komiyama Atsushi1

Affiliation:

1. *Pediatrics,

2. †Blood Transfusion,

3. ‡Parasitology, and

4. §Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan;

5. ¶Nagano Children’s Hospital, Toyoshina, Japan; and

6. ∥Department of Laboratory Sciences, School of Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan

Abstract

AbstractThe induction of IgE switching in B cells requires several signals given by cytokines and cell contact-delivered signals. Here, we investigated the role of CD27/CD70 interaction in B cell IgE synthesis. The addition of CD27 ligand (CD70) transfectants to B cell cultures increased the IgE synthesis synergistically in the presence of IL-4 plus anti-CD40 mAb (anti-CD40). The effect of CD70 transfectants was dose dependent and was completely blocked by anti-CD70 mAb. CD27+ B cells had the ability to produce IgE, which was increased by contact with CD70 transfectants, whereas CD27− B cells did not produce IgE. CD27/CD70 interaction enhanced B cell proliferation in the presence of IL-4 or IL-4 plus anti-CD40. The augmentation of B cell proliferation by CD70 transfectants was apparent in CD27+ B cells, but was mild in CD27− B cells. The helper activity for IgE synthesis by the CD27/CD70 interaction did not contribute to the enhancement of germline ε transcripts. Flow cytometric and morphological analyses demonstrated that the addition of CD70 transfectants to B cell cultures remarkably promoted differentiation into plasma cells in the presence of IL-4 and CD40 signaling. Finally, CD27 cross-linking resulted in the up-regulation of positive regulatory domain I-binding factor-1. Taken together, our findings indicate that signaling via CD27 on B cells induces IgE synthesis, in cooperation with IL-4 and CD40 signaling, by promoting the generation of plasma cells through up-regulation of positive regulatory domain I-binding factor-1.

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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