Interleukin-24 inhibits the plasma cell differentiation program in human germinal center B cells.
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.
Maarof
Ghyath
G
Inserm Unité 764, IFR13, Université Paris-Sud XI, Clamart, Centre Hospitalier, Universitaire (CHU) de Nancy, Nancy Université, Nancy, France.
Bouchet-Delbos
Laurence
L
Gary-Gouy
Hélène
H
Durand-Gasselin
Ingrid
I
Krzysiek
Roman
R
Dalloul
Ali
A
D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D015870:Gene Expression; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000099180:Interleukin-24
D019013:CD40 Antigens; D007378:Interleukins; D034741:RNA, Small Interfering; D000099180:Interleukin-24