How does our body manage to make a vast array of diverse anitibodies?

Antibodies are proteins, which are encoded by genes; one gene one protein.  The human genome contains fewer than 50,000 genes, and yet we seem to have capability to make unlimited diverse antibodies as the need arises.  This puzzle was solved by Susumu Tonegawa who was awarded a Nobel Prize in Medicine in 1987.

Our immune system has evolved a unique genetic mechanism that enables it to generate virtually unlimited number of different antibodies by joining separate gene segments together before the codes (nucleotides sequence) are transcribed into messenger RNA, which are then translated into a different language—sequence of amino acids of a protein, or antibody in this case.

We all know it was Salvador Luria who sent James Watson to to meet with Crick.  It is less well known that both Luria and Renato Dulbecco had a strong impact on Tonegawa’s career.  In his autobiography (A Slot Machine, A Broken Test Tube), Luria wrote about his stay at Indiana University,

And my very first graduate student in Bloomington, in 1947, was a thin young man named Jim Watson, of twice double-helix fame—for his discovery of DNA structure (for which he shared a Nobel Prize with Francis Crick) and for the excellent book he wrote about that discovery.  With me Jim worked on the reactivation [of killed bacteriophage] phenomenon.  My role in arranging Watson’s fateful move from Copenhagen to Cambridge has been recounted many times in books on the DNA story.  That I arranged the move is true; that it was arranged when I met the British spectroscopist John Kendrew, and that John and I were congenial because we both were socialists is also true.

When the U.S. Immigration wouldn’t extend his stay in the States, it was Dulbecco sent him to to work with Niels Jerne.  On his Nobel Lecture in 1987, Tonegawa began with

One day in the fall of 1970, I received an airmail letter from Renato Dulbecco who was travelling in Europe. At that time I was a postdoctoral fellow in his laboratory at the Salk Institute. The letter, written on stationery of the Hotel Hassler in Rome said:

“Dear Susumu,

I don’t know what arrangements you have made for after your departure from La Jolla [where Salk Institute is] at the end of the year but I would like to mention to you another possibility. The Institute of  Immunology in Basel, Switzerland will start operating in a month. They already have an excellent collection of immunologists, but have not yet built an adequate background in molecular biology. I talked about you to Niels Jerne, the Director, and they are interested in having you there …

Thanks partly to this remarkably prophetic letter and partly to the immigration law that prevented me from remaining in the U.S.A., in February 1971 I found myself in this cozy Swiss town almost completely surrounded by immunologists.

Luria later recruited Tonegawa to MIT where he was at the time of his Nobel Prize award.  Tonegawa also bridged the molecular biology to immunology.