Cross-linking of MHC class II molecules with anti-MHC class II antibody or epitope peptide prevents resting B lymphocyte differentiation by inhibiting NF-kappaB-dependent gene expression.
To understand the mechanism(s) involved in anti-MHC class II antibody-mediated inhibition of B lymphocyte differentiation, we investigated the influence of anti-MHC class II antibody treatment on the gene expression of IL-6 in resting B lymphocytes, which had been known to be one of the most important cytokines involved in B cell physiology. The level of the IL-6 mRNA expression in the LPS-stimulated resting B cells was remarkably reduced by treatment of the corresponding anti-MHC class II antibodies. The inhibition was exerted in haplotype-specific and dose-dependent manners. Similarly, MHC class 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 anti-MHC class II antibody and MHC class II-restricted epitope peptide inhibited, in haplotype-specific and dose-dependent manners, the activation of NF-kappaB, which had been known to be one of the critical transcription factors involved in the IL-6 gene expression. Interestingly, however, exogenous addition of the recombinant IL-6 did not reverse this inhibitory effect by the anti-MHC class II antibody. These results suggest that conjugation of the MHC class II molecules by the anti-MHC class II antibody inhibited B cell differentiation, possibly through the interruption of signaling pathways leading to the IL-6 gene expression via NF-kappaB activation in B lymphocytes.
Kim
J
J
Division of Biological Sciences and the Institute for Molecular Biology and Genetics, Chonbuk National University, Chonju, Korea.
Kim
H R
HR
Bae
J L
JL
Kim
D H
DH
Ki
H J
HJ
Lee
H K
HK
Choi
S H
SH
Jang
Y S
YS
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010455:Peptides