Cross-linking of MHC class II molecules with anti-MHC class II antibody orepitope peptide prevents resting B lymphocyte differentiation by inhibiting NF-kappa B-dependent gene expression

To understand the mechanism(s) involved in anti-MHC class II antibody-media ted inhibition of B lymphocyte differentiation, we investigated the influen ce of anti-MHC class II antibody treatment on the gene expression of IL-6 i n resting B lymphocytes, which had been known to be one of the most importa nt cytokines involved in B cell physiology. The level of the IL-6 mRNA expr ession in the LPS-stimulated resting B cells was remarkably reduced by trea tment of the corresponding anti-MHC class II antibodies. The inhibition was exerted in haplotype-specific and dose-dependent manners. Similarly, MHC c lass II-restricted epitope peptides, when applied as a dimer form, revealed haplotype-specific and dose-dependent inhibitory effects on the IL-6 gene expression by the LPS-stimulated B cells. In addition, treatment of the ant i-MHC class II antibody and MHC class II-restricted epitope peptide inhibit ed, in haplotype-specific and dose-dependent manners, the activation of NF- kappaB, which had been known to be one of the critical transcription factor s involved in the IL-6 gene expression. Interestingly, however, exogenous a ddition of the recombinant IL-6 did not reverse this inhibitory effect by t he anti-MHC class II antibody. These results suggest that conjugation of th e MHC class II molecules by the anti-MHC class II antibody inhibited B cell differentiation, possibly through the interruption of signaling pathways l eading to the IL-6 gene expression via NF-kappaB activation in B lymphocyte s.