Expression and function of IL-12 and IL-18 receptors on human tonsillar B cells.
IL-12 activates murine and human B cells, but little information is available as to the expression and function of IL-12R on human B lymphocytes. Here we show that the latter cells, freshly isolated from human tonsils, expressed the transcripts of both beta1 and beta2 chains of IL-12R and that beta2 chain mRNA was selectively increased (4- to 5-fold) by incubation with Staphylococcus aureus Cowan I bacteria or IL-12. B cell stimulation with IL-12 induced de novo expression of the transcripts of the two chains of IL-18R, i.e., IL-1 receptor-related protein and accessory protein-like. Functional studies showed that both IL-12 and IL-18 signaled to B cells through the NF-kappaB pathway. In the case of IL-12, no involvement of STAT transcription factors, and in particular of STAT-4, was detected. c-rel and p50 were identified as the members of NF-kappaB family involved in IL-12-mediated signal transduction to B cells. IL-12 and IL-18 synergized in the induction of IFN-gamma production by tonsillar B cells, but not in the stimulation of B cell differentiation, although either cytokine promoted IgM secretion in culture supernatants. Finally, naive but not germinal center or memory, tonsillar B cells were identified as the exclusive IL-12 targets in terms of induction of NF-kappaB activation and of IFN-gamma production.
Airoldi
I
I
Laboratory of Oncology, G. Gaslini Institute, Genoa, Italy. laboncologia@ospedale-gaslini.ge.it
Gri
G
G
Marshall
J D
JD
Corcione
A
A
Facchetti
P
P
Guglielmino
R
R
Trinchieri
G
G
Pistoia
V
V
D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism* / Q000494:pharmacology; D020382:Interleukin-18 / Q000378:metabolism* / Q000494:pharmacology; D053727:Interleukin-18 Receptor alpha Subunit; D008213:Lymphocyte Activation / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; C508438:IL12RB1 protein, human; C508439:IL12RB2 protein, human; C508572:IL18R1 protein, human; D007132:Immunoglobulin Isotypes; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D016328:NF-kappa B; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators; D018664:Interleukin-12; D007371:Interferon-gamma