No sting in this tale
Antibodies are the flashing beacons of the human immune system. By coating foreign invaders, they mark them out for removal by immune system cells such as macrophages and neutrophils. These foreign invaders can be bacteria, viruses, parasites, toxins or, as scientists have now shown, even bee sting proteins.
Antibodies are produced by immune system cells known as B lymphocytes, with every individual B lymphocyte cell capable of producing a different antibody. Biologists estimate that the lymphocytes in an average adult human are collectively able to produce up to a million trillion different antibodies.
They are able to do this by virtue of an ingenious genetic mechanism, in which a selection of antibody genes randomly combines in each lymphocyte to produce a unique antibody. These B lymphocytes are then sent circulating in the blood stream to look for molecules that naturally bind with their antibodies, which they express on their surfaces.
Before they are permitted to go out, however, the immune system first checks each B lymphocyte to see whether its specific antibody is able to bind with any molecules produced by the body’s own cells. If it can, then that B lymphocyte is destroyed. This means that if the antibody on the surface of a B lymphocyte binds with a molecule, known as an antigen, then that molecule must come from a foreign invader. Often, it’s a protein from the cell wall of a bacteria or the protein coat of a virus.
This immediately sets the alarm bells ringing. The B lymphocyte reproduces rapidly and it and all its progeny start producing loads of copies of the antibody, which they release into the body. These antibodies then naturally bind with the protein on the surface of the bacteria or virus, marking them out for removal by macrophages and neutrophils.
Scientists can create antibodies to order by injecting a specific antigen into laboratory mice, which have a similar immune system to us. They extract the resultant B lymphocytes and merge them with cancer cells known as myeloma, creating hybridomas that can both produce the antibody and reproduce indefinitely. These hybridomas are then grown in bioreactors and the antibodies harvested. But now a team of US and Japanese scientists led by Kenneth Shea from the University of California, Irvine, has gone one step further, by creating completely artificial antibodies.
To do this, they took advantage of a technique known as molecular imprinting. This essentially involves coating molecules in plastic and then removing the molecules, leaving behind a perfect imprint of the molecule in the plastic. This perfect imprint can then be used to detect the original molecule.
Such molecular imprinted polymers, as they are known, have been created for various non-biological molecules. Developing a version of this technique that is delicate enough to work with biological molecules such as proteins has proved more of a challenge. But this is what Shea and his team managed in 2008, creating plastic particles just 30–40nm in size that each possessed an imprint of the protein melittin, which is the major component of bee sting. They described this work in the Journal of the American Chemical Society.
Now, in another paper in the Journal of the American Chemical Society, they report that these nanoparticles are able to act as artificial antibodies. Melittin damages cells and so at high enough doses it can kill small mammals such as mice. Shea and his team injected mice with these lethal doses, but in some they also injected the imprinted nanoparticles and in others they injected nanoparticles that didn’t possess the imprint.
Mice injected with the imprinted nanoparticles were far less likely to die than the other mice, indicating that the nanoparticles were indeed acting as antibodies. To see exactly what was going on, the scientists labelled the imprinted nanoparticles and the melittin proteins with fluorescent dyes. They discovered that, as suspected, the imprinted nanoparticles were coating the melittin, which was then being removed by macrophages.
‘Never before have synthetic antibodies been shown to effectively function in the bloodstream of living animals,’ says Shea. ‘This technique could be utilised to make plastic nanoparticles designed to fight more lethal toxins and pathogens.’
