Ligation of MHC class II molecules differentially upregulates TNF beta gene expression in B cell lines of different MHC class II haplotypes.

Although the production of selected cytokines by B cells is important for their regulation, little is known about MHC class II-induced cytokine expression in these cells. We designed the present studies to investigate MHC class II-mediated TNF-beta gene expression in 19 EBV-transformed homozygote B cell lines at similar stage of differentiation but presenting different MHC class II haplotypes. Our results demonstrate that in contrast to PMA, engagement of MHC class II with staphylococcal enterotoxin A (SEA), a natural ligand, or with anti-HLA-DR mAb L243, stimulates TNF-beta gene expression in some but not all B cell lines. The differential stimulation of TNF-beta gene expression via MHC class II was not due to the cells MHC class II expression level, nor to their capacity to bind the ligands as evidenced by SEA binding affinity studies. Together these results demonstrate that ligation of MHC class II molecules can stimulate TNF-beta gene expression in a B cell line-dependent manner. The differential cytokine gene expression might be due to an influence of MHC class II haplotype either by a linkage disequilibrium with TNF-beta gene or by a differential association with effector or cell surface molecules.