Plasmid DNA and IL-4 modulate expression of mHC class I and costimulatory molecules in B lymphocytes.
B lymphocytes are capable of spontaneous internalization of plasmid (p)DNA, an event that set in motion the antigen-presenting function in this class of hemopoietic cells. Previously, we showed that priming of CD8 T lymphocytes by spontaneously transgenic B lymphocytes requires T-cell help, and that this can be replaced by soluble IL-4. To better understand this phenomenon we studied the relative role of pDNA and IL-4 on the expression of MHC-I and a panel of critical costimulatory molecules (CD40, CD80, CD86, OX40L, and LAG-3). Whereas upregulation of MHC-I is contributed by pDNA, IL-4 mainly upregulates CD86 and to a lesser degree CD40. The two effects appear to be independent. In addition, however, it was found that IL-4 stabilizes MHC-I transcription in lymphocytes after spontaneous transgenesis with pDNA. These results further our understanding of events that take place in specialized mammalian cells after exposure to pDNA. They also point to the fact after pDNA internalization that the antigen-presenting function of B lymphocytes can be complemented by IL-4, a cytokine normally produced by activated CD4 T cells.
Frazzi
Raffaele
R
The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093-0815, USA.
Zanetti
Maurizio
M
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053278:OX40 Ligand / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects*
D015703:Antigens, CD; D053278:OX40 Ligand; D015847:Interleukin-4; D004247:DNA