PubMed · 11221521
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J Abay, J Warner. 2001. Asthma's link with affluence.. https://pubmed.ncbi.nlm.nih.gov/11221521/
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B-cell development to antibody-producing plasma cells requires the concerted function of a large number of genes and proteins. Genome-level expression profiling during human B-cell maturation was studied in anti-immunoglobulin M-stimulated Ramos cells. cDNA microarrays were used to follow changes in the transcriptome over several days. Close to 1500 genes had significantly altered expression at least at one time point. The genes were organized into clusters based on expression profiles and were further characterized based on the functions of the coded proteins. Several groups of genes important for B cells were analyzed. Here we concentrate on genes involved in signal transduction and cytokines and their receptors. The results provide knowledge on the development of humoral immunity. Several new genes were found to be essential for B-cell development. They can be used as targets for research and possibly for drug development.
New immunosuppressive drugs are extensively being investigated for their effect on T-cell immunity, with far less being known about their effect on the humoral immune response. In view of the experimental and clinical evidence that humoral immunity contributes to acute and chronic rejection, we investigated post-transplant production of anti-vimentin and anti-HLA antibodies in 86 patients who were part of a worldwide clinical trial for mycophenolate mofetil in cardiac transplantation. The results demonstrate that patients taking MMF instead of azathioprine generated significantly fewer de novo anti-vimentin antibodies.
Several naturally occurring variants of immunogenic T cell epitopes were identified within the hepatitis B surface antigen (HBsAg). The effect of these variants on the cellular immune response was studied in individuals vaccinated against HBV. Class-II restricted T-cell responses of 30 vaccinees were analyzed after stimulation of peripheral blood mononuclear cells (PBMCs) with 4 synthetic peptides representing the 4 T-cell epitopes of HBsAg known as of yet. The 2 epitopes P1 (aa 16-33) and P4 (aa 213-226) could be identified as the dominant ones in our vaccinees by proliferation assays and enzyme-linked immunospot assays. Responses to these epitopes were compared with responses to their naturally occurring variants found in HBV isolates of chronic virus carriers. Three of 11 variants of epitope P4 led to a complete loss of T-cell reactivity in 4 of 10 donors, all of whom reacted well to the corresponding wild-type sequence. The remaining 6 donors recognized these variants as well as the vaccine epitope. Similarly, 3 P1-variants of the 12 found induced only a significantly reduced reactivity in 4 of 10 donors, whereas they led to a normal response in the other 6 individuals. Stimulation of T cells also induced the secretion of antibody to HBsAg (anti-HBs) by specific B cells; however, those peptides that failed to activate T cells were also unable to cause any significant anti-HBs production. In conclusion, our results suggest an immune escape of certain mutant strains of HBV in vaccinated individuals could exist at the T-cell level.