Researchers develop new method to generate human antibodies

A team of scientists developed a method to rapidly produce specific human antibodies in the laboratory.

The paper regarding the technique was published on 24 July 2017 in The Journal of Experimental Medicine.

The revolutionary technique could speed the production of antibodies to treat a wide range of diseases and facilitate the development of new vaccines.

How the technique was achieved?

• Antibodies are produced by the body's B cells to fight off infections by bacteria, viruses, and other invasive pathogens. When an individual B cell recognizes a specific pathogen-derived "antigen" molecule, it can proliferate and develop into plasma cells that secrete large amounts of antibody capable of binding to the antigen and fending off the infection.

• Researchers sought to replicate this process in the laboratory to produce specific antibodies from B cells isolated from patient blood samples. However, in addition to encountering a specific antigen, B cells need a second signal to start proliferating and developing into plasma cells. This second signal can be provided by short DNA fragments called CpG oligonucleotides, which activate a protein inside B cells named TLR9. However, treating patient-derived B cells with CpG oligonucleotides stimulates every B cell in the sample, not just the tiny fraction capable of producing a particular antibody.

• A team of researchers led by Facundo Batista, from the Francis Crick Institute in London and the Ragon Institute of MGH, MIT, and Harvard, have been able to produce specific human antibodies in the laboratory by treating patient-derived B cells with tiny nanoparticles coated with both CpG oligonucleotides and the appropriate antigen.

• With the technique, CpG oligonucleotides are only internalized into B cells that recognize the specific antigen, and these cells are therefore the only ones in which TLR9 is activated to induce their proliferation and development into antibody-secreting plasma cells.

• The team successfully demonstrated their approach using various bacterial and viral antigens, including the tetanus toxoid and proteins from several strains of influenza A.

• In each case, the researchers were able to produce specific, high-affinity antibodies in just a few days. Some of the anti-influenza antibodies generated by the technique recognized multiple strains of the virus and were able to neutralize its ability to infect cells.

• The procedure does not depend on the donors having been previously exposed to any of these antigens through vaccination or infection. The researchers were able to generate anti-HIV antibodies from B cells isolated from HIV-free patients.

• The team believed that their approach will help researchers rapidly generate therapeutic antibodies for the treatment of infectious diseases and other conditions such as cancer.

What are antibodies?

• An antibody is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as bacteria and viruses.

• It is also known as an immunoglobulin.

• The antibody recognizes a unique molecule of the harmful agent, called an antigen, via the Fab's variable region.

• Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly. Depending on the antigen, the binding may impede the biological process causing the disease or may activate macrophages to destroy the foreign substance.

• The production of antibodies is the main function of the humoral immune system.

• Antibodies are secreted by B cells of the adaptive immune system, mostly by differentiated B cells called plasma cells.

• Antibodies can occur in two physical forms, a soluble form that is secreted from the cell to be free in the blood plasma, and a membrane-bound form that is attached to the surface of a B cell and is referred to as the B-cell receptor (BCR).