Heterogeneous expression of interleukin-18 and its receptor in B-cell lymphoproliferative disorders deriving from naive, germinal center, and memory B lymphocytes.
OBJECTIVE
Dysregulated cytokine/cytokine receptor expression may occur in B-cell lymphoproliferative disorders. Little information is available on interleukin-18 receptor (IL-18R) and IL-18 expression in normal and malignant B cells. Our purpose was to investigate this issue in human naive, germinal center (GC) and memory B cells, and in their neoplastic counterparts.


METHODS
We have evaluated IL-18 expression and production in tonsil naive, GC, and memory B cells and in their presumed neoplastic counterparts by reverse transcription-PCR and ELISA. Moreover, IL-18Ralpha and beta expression was investigated in the same cells by reverse transcription-PCR, flow cytometry, and immunohistochemistry.


RESULTS
We found that: (a) IL-18 mRNA was expressed in tonsil naive, GC, and memory B cells. Bioactive IL-18 was secreted by naive and GC, but not by memory B cells; (b) IL-18Ralpha and beta transcripts were expressed in the three B-cell subsets. IL-18Ralpha was detected on the surface of naive, GC, and memory B lymphocytes, and IL-18Rbeta was detected on GC and memory, but not naive, B cells; (c) mantle zone, follicular, marginal zone, Burkitt lymphoma (BL), and B-cell chronic lymphocytic leukemia (B-CLL) cells expressed IL-18 mRNA. B-CLL and BL cells did not produce bioactive IL-18; and (d) lymphoma B cells displayed heterogeneous expression of either or both IL-18R chain mRNA. In contrast, B-CLL cells expressed both IL-18R chains at the mRNA and protein levels.


CONCLUSIONS
Dysregulated expression of IL-18 and/or IL-18R in chronic B-cell lymphoproliferative disorders may sometimes contribute to tumor escape from the host immune system.
Airoldi
Irma
I
Laboratories of Oncology and Pathology, G. Gaslini Institute, Genoa, Italy, and Laboratory of Pathology, St. Andrea Hospital, La Spezia, Italy. laboncologia@ospedalegaslini.ge.it
Raffaghello
Lizzia
L
Cocco
Claudia
C
Guglielmino
Roberta
R
Roncella
Silvio
S
Fedeli
Franco
F
Gambini
Claudio
C
Pistoia
Vito
V
D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007156:Immunologic Memory; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit; D015448:Leukemia, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053724:Receptors, Interleukin-18; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D020033:Protein Isoforms; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18