In the latest issue of Nature Medicine, a group of German scientists from the University Hospital Großhadern is describing a method to match circulating immunoglobulins to their B-cells source.
Max Planck Society for the Advancement of Science reports:
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.
Yet, where do these antibodies come from? Do they stem from the relatively few B-cells found in the liquor? Or do they have their origin, like other antibodies, in the blood or the lymphatic organs such as the spleen, the lymph nodes or the bone marrow? With such an origin, the antibodies would need to breach the blood-brain barrier in order to reach the liquor. Although these questions can essentially aid our understanding of multiple sclerosis, they remained long unaddressed. Now, scientists of the Max Planck Institute of Neurobiology and their Munich colleagues succeeded in developing a procedure which allows the allocation of antibodies to their cells of origin. To achieve this, the scientists took advantage of the vast variety of B-cells. They 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. Moreover, the high genetic variability in certain areas of the DNA showed that the liquor B-cells already made contact with their target structures in the nervous system.
“The next step is now the assembly of the fragments into complete antibodies, which should allow us to identify their target structures in the nervous system” explains Klaus Dornmair, who supervised the study. So far, the targets of most antibodies are still unknown. The identification of target structures could eventually allow the removal of antibodies with the most detrimental effects, which in turn could mitigate multiple sclerosis effects. “An additional highlight of our new procedure is the fact that it’s not restricted to multiple sclerosis analyses”, reports Klaus Dornmair. The relatively quick and easy procedure should also allow the allocation of antibodies and B-cells in other inflammatory and autoimmune diseases and thus aid our understanding of underlying processes.
Press release: New procedure enables the matching of antibodies to their source cells …
Abstract in in Nature Medicine: Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis doi:10.1038/nm1714
