Interleukin-24 inhibits the plasma cell differentiation program in human germinal center B cells
| Autor: | Roman Krzysiek, Ali Dalloul, Ghyath Maarof, Ingrid Durand-Gasselin, Laurence Bouchet-Delbos, Hélène Gary-Gouy |
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| Rok vydání: | 2010 |
| Předmět: |
Cellular differentiation
Plasma Cells Immunology B-cell receptor Naive B cell Gene Expression Plasma cell Biochemistry Plasma cell differentiation medicine Centroblasts Humans CD40 Antigens RNA Small Interfering Cells Cultured B-Lymphocytes CD40 Base Sequence biology Interleukins Germinal center Cell Differentiation Cell Biology Hematology Germinal Center Cell biology medicine.anatomical_structure biology.protein RNA Interference |
| Zdroj: | Blood. 115:1718-1726 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2009-05-220251 |
| Popis: | Complex molecular mechanisms control B-cell fate to become a memory or a plasma cell. Interleukin-24 (IL-24) is a class II family cytokine of poorly understood immune function that regulates the cell cycle. We previously observed that IL-24 is strongly expressed in leukemic memory-type B cells. Here we show that IL-24 is also expressed in human follicular B cells; it is more abundant in CD27+ memory B cells and CD5-expressing B cells, whereas it is low to undetectable in centroblasts and plasma cells. Addition of IL-24 to B cells, cultured in conditions shown to promote plasma cell differentiation, strongly inhibited plasma cell generation and immunoglobulin G (IgG) production. By contrast, IL-24 siRNA increased terminal differentiation of B cells into plasma cells. IL-24 is optimally induced by BCR triggering and CD40 engagement; IL-24 increased CD40-induced B-cell proliferation and modulated the transcription of key factors involved in plasma cell differentiation. It also inhibited activation-induced tyrosine phosphorylation of signal transducer and activator of transcription-3 (STAT-3), and inhibited the transcription of IL-10. Taken together, our results indicate that IL-24 is a novel cytokine involved in T-dependent antigen (Ag)–driven B-cell differentiation and suggest its physiologic role in favoring germinal center B-cell maturation in memory B cells at the expense of plasma cells. |
| Databáze: | OpenAIRE |
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