IL-10 enhances B-cell IgE synthesis by promoting differentiation into plasma cells, a process that is inhibited by CD27/CD70 interaction.
Interleukin-10 (IL-10) is a major regulatory cytokine of inflammatory responses that is considered to play an important role in specific immunotherapy. However, whether IL-10 enhances or inhibits B-cell IgE production has remained a matter of contention. To clarify the effect of IL-10 on IgE synthesis in the presence of IL-4 and CD40 signalling, we examined B-cell proliferation, germline epsilon transcripts and plasma cell differentiation. In addition, the effect of CD27 signalling on IgE synthesis in the presence of IL-10, IL-4 and CD40 signalling was investigated. IL-10 facilitated the production of IgE in mononuclear cells and highly purified B-cells, enhanced B-cell proliferation and, most importantly, promoted the generation of plasma cells. However, IL-10 did not enhance expression of germline epsilon transcripts. The addition of CD27 signalling through the use of CD32-CD27 ligand (CD70) double transfectants significantly diminished the B-cell proliferation, IgE synthesis and plasma cell differentiation enhanced by IL-10. IL-10 enhances B-cell IgE production by promoting differentiation into plasma cells. CD27/CD70 interactions under IL-10 and sufficient CD40 cosignalling exert the opposite effect on IgE synthesis. The results of this study indicate that precautions are critical when planning immunotherapy using IL-10 in IgE-related allergic diseases.
Department of Paediatrics, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.
N
N
Kobayashi
H
H
Nagumo
K
K
Agematsu
D000328:Adult; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D053282:CD27 Ligand; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology*; D010950:Plasma Cells / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*
D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D007073:Immunoglobulin E