While reading articles about monoclonal antibodies in New York Times, I came across “New
method of creating antibodies hailed as a research aid”, published on
12/8/1989, in which there was a paragraph:
“A human is born with about 100 million
different antibodies,
ready to meet an invasion. Although antibodies can be extracted from human
tissue, they do not survive outside the body under laboratory conditions.”
The author of the article, Sandra Blakeslee, a respectable NY Times science writer. She is Northwestern U. and U.C. Berkeley
educated with a major in political science.
I think
this statement is not quite correct; a human is not born with about 100
million antibodies, instead a human is capable for producing “100 million” (or
more precisely, limitless) different antibodies. An antibody is produced by B lymphocyte in
response to an invasion by foreign agent, such as virus or bacteria or any toxin.
Antibody will seek the foreign invader and mark it for destruction. So we’re not born with antibodies; it was
produced in response to foreign invasion.
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. If each antibody were coded by a separate and
distinct gene, a B cell’s genome would have to carry an enormous and improbably
large number of antibody genes. And we know that is not the case; it is a fact.
This puzzle was solved by
Susumu Tonegawa who was awarded a Nobel Prize in Medicine in 1987. It turns out that our immune system has evolved
a unique genetic mechanism: Various segments of an antibody gene can be cut and
paste/fused 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.
Susumu
Tonegawa wrote an article of “The molecules of the immune system” in
10/1/1985 Scientific American, two
years before he was awarded the Nobel Prize in Medicine. The diagram below is taken from the article.
ASSEMBLY
OF AN ANTIBODY GENE from scattered fragments is done in two stages, shown for a
kappa light chain. First randomly selected V and J segments are fused by
enzymes that delete all the DNA lying between them. Here the gene segments
labeled V3, V4 and J1 are deleted, bringing together V2 and J2. Next the entire length of DNA from the start
of V2 to the end of the C gene is transcribed into RNA. Standard RNA-splicing
enzymes, which take part in the expression of many genes, excise all the RNA
from the end of h to the start of C. The resulting sequence of messenger RNA is
translated into protein.
 |
| Tonegawa in 2013--still at MIT |
I wrote a post in my blog on 5/31/2007 (“How does our body
manage to make a vast array of diverse antibodies?” There are some interesting stories. There was a twist of fate that he was forced
to move to the Basal Institute of Immunology in Switzerland in 1972. By ‘kicking him out of the United States’,
the U.S. Immigration Service may unwittingly helped advance of science.
Most of his work was published in the Proceedings of the National Academy of Sciences between
1976-1978. He so dominated in this field
that he was a single Nobel Prize in Medicine winner in 1987. With few exceptions the Nobel Prizes in
sciences were shared by two or three laureates.
It was Salvador Luria (like Enrico Fermi, my another Italian
American idol) who recruited Susumu Tonegawa to MIT in 1981, adding another
Nobel laureate to its long list in 1987—a windfall to MIT.
“How does our body manage to make a vast array of diverse
antibodies?”
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