| MadSci Network: Immunology |
Susumu Tonegawa was awarded the Nobel Prize in 1987 for his landmark studies on the molecular biology of antibodies. Antibodies are proteins which circulate in the blood and allow the recognition of foreign particles (viruses, bacteria, fungus, parasites) by the body. Before Tonegawa's studies, it was unclear how the body could have the ability to generate an almost infinite number of antibodies with distinct structures, allowing the body to recognize any possible foreign particle. The problem came from the fact that humans only have a certain amount of DNA in every cell, and if each antibody was coded for by a separate gene (a portion of DNA) we would need more DNA than each cell actually has. Tonegawa showed that every cell in the body has a stretch of DNA devoted to coding for antibodies, but that the ability to create diverse antibodies comes from the special ability of certain cells to recombine this DNA in new ways. These cells are the so called B lymphocytes, special white blood cells which are the ones circulating through the body producing antibodies. Each B cell reshuffles the stretch of DNA which codes for antibody, thus producing an antibody with a structure unlike that made by any other B cell. Tonegawa's research opened up the idea of cells having the ability to alter their own DNA. By understanding what is required for a cell to do this DNA recombination, medical doctors now have an understanding of certain human immunodeficiencies, diseases in which a person's immune system can't respond properly to infections. Some of these immunodeficiencies are due to the fact that the B lymphocytes can't properly recombine their DNA, leaving the person unable to make diverse antibodies to possible infections. Tonegawa's research has also clarified how certain mutations in DNA can lead to cancers of B cells. Often times in these particular cancers, genes which are known to cause cancer (so called oncogenes) happen to get incorporated into the stretch of DNA which normally codes for antibodies. The reason why these genes happen to get incorporated in this particular area of DNA is because as Tonegawa showed, this area of DNA is undergoing recombination. Cuts are being made and then pieces of DNA are rejoined together. While all of this is going on, sometimes an oncogene happens to get incorporated in this recombination. Once an oncogene gets incorporated here, it can be overexpressed (in other words, more of the protein for which this gene codes gets made than should be made). Such overexpression leads to unregulated growth of this B cell, thus giving the patient a B cell cancer (called a leukemia or lymphoma). Hope that helped... Brian Edelson MD/PhD Student School of Medicine edelsonb@medicine.wustl.edu
Try the links in the MadSci Library for more information on Immunology.