Impact of IL-6 receptor inhibition on human memory B cells in vivo: impaired somatic hypermutation in preswitch memory B cells and modulation of mutational targeting in memory B cells
| Autor: | Hans-Peter Tony, Thomas Seibold, Hermann Einsele, Petra Roll, Thomas Dörner, Khalid Muhammad, Stefan Kleinert |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Immunology B-Lymphocyte Subsets Immunoglobulin Variable Region Somatic hypermutation Antibodies Monoclonal Humanized Receptors Tumor Necrosis Factor General Biochemistry Genetics and Molecular Biology Etanercept Arthritis Rheumatoid Rheumatology Humans Immunology and Allergy Prospective Studies Gene Rearrangement B-Lymphocyte Interleukin 6 Receptor Aged biology Tumor Necrosis Factor-alpha Gene rearrangement Middle Aged Receptors Interleukin-6 Antirheumatic Agents Immunoglobulin G Monoclonal Interleukin-6 receptor biology.protein Cancer research Female Tumor necrosis factor alpha Somatic Hypermutation Immunoglobulin Antibody Immunologic Memory |
| Zdroj: | Annals of the Rheumatic Diseases. 70:1507-1510 |
| ISSN: | 0003-4967 |
| Popis: | Interleukin 6 (IL-6) receptor (IL-6R) inhibition by tocilizumab is a novel anti-inflammatory therapy for rheumatoid arthritis (RA) patients. As IL-6 is a late differentiation factor of B cells the authors asked if IL-6R inhibition impacts on the mutational differentiation of human memory B-cell antigen receptors in vivo.1733 immunoglobulin receptors (IgR) of single cell sorted preswitch and postswitch memory B cells were prospectively analysed from 11 RA patients under IL-6R inhibition (7 patients) or tumour necrosis factor (TNF) inhibition (4 patients).The results show a reduced mutational frequency in IgR of preswitch memory B cells (p=0.0001) during week 12, week 24 and 1 year of tocilizumab therapy. Mutational hotspot RGYW/WRCY motifs indicated significantly decreased targeting (p0.05) in preswitch and postswitch memory B cells. Anti-TNFα therapy had no effect on mutational frequency and mutational hotspot targeting motifs in memory B-cell subsets.These data suggest that preswitch and postswitch memory B cells are susceptible to IL-6R inhibition in vivo. Acquisition of mutations was substantially altered in preswitch memory B cells, while targeting of mutational hotspots affected preswitch and postswitch memory B cells. The results indicate that preswitch and postswitch memory B cells have a differential dependence on the IL-6/IL-6R system for differentiation, which can be influenced by tocilizumab in vivo. |
| Databáze: | OpenAIRE |
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