Immunologists know that it is sometimes possible to prevent an immune
response to a protein. But the new experiments, described last month at a
Keystone Symposium on immunology in Hilton Head, South Carolina, are the first
to turn off a response that has already started. This is important for
researchers working on autoimmune diseases, which develop without warning.
鈥淧eople don鈥檛 go to their doctor and say, `I think I鈥檓 going to develop an
autoimmune disease in 10 years鈥�,鈥� says David Scott of the American Red Cross in
Rockville, Maryland.
The immune system鈥檚 T and B cells only attack proteins when they appear in a
certain way鈥攐n the surface of antigen-presenting cells, and when some
other biochemical warning signal is present (New 女生小视频, Science, 30
March, p 14). So the immune system can sometimes ignore proteins if, for
example, they are released by B cells.
Scott and his colleague Elias Zambidis bred mice carrying B cells that were
genetically engineered so that an antibody they secreted called immunoglobulin G
incorporated a protein from a virus that infects bacteria. When the researchers
injected these animals with the foreign protein, there was no immune response.
And when they took B cells from these animals and injected them into normal
mice, they also ignored the protein.
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But the real surprise came when Scott and Zambidis injected the altered B
cells into mice that had already been 鈥減rimed鈥� to attack the viral protein. The
animals suddenly began to produce less antibodies to the protein. 鈥淭o our
knowledge, no one has done this before,鈥� says Scott.
This sharp drop in antibody production only occurred when the altered B cells
had first been exposed to a bacterial toxin that made them produce large amounts
of the immunoglobulin. Unstimulated B cells failed to switch off the immune
response to the protein. Scott does not know if the animals鈥� immune systems were
lulled into a state of 鈥渢olerance鈥�, or whether the large doses of viral protein
simply exhausted the animals鈥� immune defences.
Daniel Mueller of the University of Minnesota, a specialist on immunological
tolerance, says the findings are 鈥減rovocative鈥�, but warns that more work is
needed before the same approach can be applied to autoimmune disease. Scott鈥檚
next aim is to repeat his mouse experiments using B cells that have been
designed to secrete immunoglobulin incorporating the nerve sheath protein that
is attacked in multiple sclerosis.
