Potential for Promising new treatment options for autoimmune diseases
Scientists at the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center have, for the first time, discovered a surprising diversity in terms of the various types of plasma cell populations in human bone marrow. Plasma cells play a pivotal role in immune defense and autoimmune reactions. Until now, these were thought to be differentiated B-cells, a component of white blood corpuscles, but not specifically divided into subgroups. As recently published in the scientific journal Blood*, plasma cells can be viewed as subpopulations with various functions, for example as regards their respective antibody production.
The main function of plasma cells and their immediate precursors ─ so-called plasmablasts ─ is to continuously supply the antibodies required for immune response. We know that particularly the plasma cells populating the bone marrow can survive for several years, which in turn contributes to the excellent immunological memory with respect to pathogens for example. In the case of autoimmune diseases such as rheumatoid arthritis, the autoantibodies target the body itself. Their cellular basis also serves to produce plasma cells, however, as autoreactive forms. "The biology of plasma cells plays a decisive role in the pathogenesis of autoimmune diseases. This is indeed a promising method that can help us to better understand the disease and assist in the development of targeted therapeutic options", says Prof. Dr. Thomas Dörner of the Medical Department, Division of Rheumatology and Clinical Immunology of the Charité. Until now, all plasma cells have been considered to be resistant vis-a-vis nearly all conventional antirheumatic therapies.
In the context of their investigation, the scientists were able to demonstrate the existence of different types of mature plasma cell-subpopulations in human bone marrow. Depending on their respective properties, the differentiated cell groups are responsible for supplying various proteins, including CD95, HLA-DR, CD56 and CD19. With regard to the expression of CD19, the researchers were able to determine that a certain plasma cell was no longer able to express CD19. For immunologists, the CD19-negative plasma cells exhibit special characteristics: they mainly produce the antibody immunoglobulin G, a particularly long-lasting and mature expression, which is mainly stored in the bone marrow. The researchers have concluded that CD19-negative plasma cells possess rather static properties, while CD19-positive plasma cells ensure immune defense in a dynamic manner, that is to say that the corresponding cells react with stability or adaptation.
"Our newly gained knowledge of the immunobiological characteristics of these heretofore unknown plasma cell subgroups will now form the basis for the future development of innovative treatment methods for autoimmune diseases", explains Prof. Dörner. In further experiments, including a cooperative project with scientists at the University of Gothenburg, patients with rheumatoid arthritis have been treated with antibodies to counter CD20-positive B-cells, in order to better control their arthritis-related inflammation. It has also been shown that such treatment influences the CD19-positive and the CD19-negative plasma cells in different ways. While the former decreased during the course of therapy, the CD19-negative plasma cells did not. Based on such significant findings, the study provides a completely new understanding of the characteristics of heretofore unknown plasma cell groups, which in the future might serve as selective treatment options for autoimmune diseases.
*Henrik E. Mei, Ina Wirries, Daniela Frölich, Mikael Brisslert, Claudia Giesecke, Joachim R. Grün, Tobia Alexander, Stefanie Schmidt, Katarzyna Luda, Anja A. Kühl, Robby Engelmann, Michael Dürr, Tobias Scheel, Maria Bokarewa,Carsten Perka, Andreas Radbruch, Thomas Dörner. A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow. Blood, Jan. 2015. doi: 10.1182/blood-2014-02-555169.
Prof. Dr. Thomas Dörner
Medical Department, Division of Rheumatology and Clinical Immunology
Charité – Universitätsmedizin Berlin
t: +49 30 450 525 241
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