Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein.
In this study, we show that IL-10 enhances in vitro the viability of purified splenic B cells. There was a two- to threefold increase in recovery of viable cells during a 15-d culture period in the presence of IL-10. This effect was abolished by neutralizing antibodies to IL-10. The survival of large splenic B cells, which mostly represent follicular center cells, was similarly increased. The in vitro rescue from spontaneous death of the latter cells is known to involve a bcl-2-dependent pathway. We therefore investigated whether IL-10 might affect bcl-2 expression. Unseparated B cells as well as large splenic B cells displayed a strong expression of bcl-2 protein by immunofluorescence at days 2-7 of culture in the presence of IL-10. Other lymphokines such as IL-2 and IL-4 were able to trigger only a transient and faint expression of bcl-2; moreover, this effect was abolished by anti-IL-10 mAb. Inasmuch as activated B cells can produce their own IL-10, this lymphokine may play a crucial role in relieving from apoptosis those B cells that encounter their antigen in B cell follicles.
Levy
Y
Y
Department of Immunopathology, Hôpital Henri Mondor, Créteil, France.
Brouet
J C
JC
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D016753:Interleukin-10; D011505:Protein-Tyrosine Kinases