Antibodies in the brain
Each of us carries an unbelievable multitude of antibodies, allowing us to survive the daily battle against pathogens. However, sometimes these antibodies go haywire and attack structures of their own body, for example nerve cells in patients with multiple sclerosis. The origin of these antibodies remained long unknown. Scientists from the University of Munich Hospital at Grosshadern and the Max Planck Institutes of Neurobiology and Biochemistry have now developed a procedure, which allows allocating antibodies to their source cells. As reported in the science journal “Nature Medicine”, this method should promote the identification of attacked target structures of multiple sclerosis and other autoimmune- and inflammatory diseases.
It is impossible for organism's immune system to know in advance which pathogens it will encounter throughout life. Therefore, antibody producing cells are created at random. The incredible variety of these B-cells arises through the combination of different genes and spontaneous mutations. A by-product of the random genesis of B-cells is that some cells will target structures of the own body. These cells are usually eliminated before they can do any harm. However, this control system fails in autoimmune diseases such as multiple sclerosis (MS), where the immune system attacks nerve cells in the brain and spinal cord. The liquid surrounding these nerve cells (the liquor) contains many antibodies in MS patients, and antibody occurrence in the liquor is used as one of the indicators for this disease.
To achieve the allocation of antibodies to their cells of origin the scientists isolated B-cells from the liquor and analyzed the genetic code of the DNA region responsible for the production of antibodies. This information then allowed the calculation of the size and weight of the respective antibody fragments produced by each analyzed B-cell. Concurrently, the scientists extracted antibodies found in the liquor and analyzed the weight of their fragments. The comparison of the two datasets left no doubt: The antibodies found in the liquor are produced by the likewise present B-cells. "The next step is now to identify the antibodies’ target structures in the nervous system" explains Klaus Dornmair, who supervised the study. This could eventually allow the removal of antibodies with the most detrimental effects in multiple sclerosis – or other autoimmune diseases.
“Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis”,
Birgit Obermeier, Reinhard Mentele, Joachim Malotka, Josef Kellermann, Tania Kümpfel, Hartmut Wekerle, Friedrich Lottspeich, Reinhard Hohlfeld, Klaus Dornmair,
Nature Medicine, May 18 2008
Dr. Klaus Dornmair
University of Munich Hospital at Grosshadern
and Max Planck Institute of Neurobiology
Phone: +49 89 8578-3566
Fax: +49 89 8995-0164