CD27/CD70 interaction augments IgE secretion by promoting the differentiation of memory B cells into plasma cells.
The 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 epsilon 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.
Nagumo
H
H
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Agematsu
K
K
Shinozaki
K
K
Hokibara
S
S
Ito
S
S
Takamoto
M
M
Nikaido
T
T
Yasui
K
K
Uehara
Y
Y
Yachie
A
A
Komiyama
A
A
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000166:cytology*; D053282:CD27 Ligand; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D005786:Gene Expression Regulation; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000502:physiology*; D010950:Plasma Cells / Q000166:cytology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; D019013:CD40 Antigens; C505771:CD70 protein, human; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C087042:PRDM1 protein, human; D015847:Interleukin-4; D007073:Immunoglobulin E; D000074462:Positive Regulatory Domain I-Binding Factor 1