Researchers develop new method to generate human antibodies

July 24, 2017, Rockefeller University Press
An electron microscopy image shows an antibody-secreting plasma cell generated using antigen- and CpG-coated nanoparticles. Credit: Sanjuan Nandin et al., 2017

An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental Medicine, could speed the production of antibodies to treat a wide range of diseases and facilitate the development of new vaccines.

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 that secrete large amounts of antibody capable of binding to the antigen and fending off the infection.

Researchers have sought to replicate this process in the laboratory to produce specific 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. But 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 this 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 isolated from HIV-free patients.

Batista and colleagues hope that their approach will help researchers rapidly generate therapeutic antibodies for the treatment of infectious diseases and other conditions such as cancer.

"Specifically, it should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals," Batista says. "In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens."

Explore further: Barrier to autoimmune disease may open door to HIV, study suggests

More information: Sanjuan Nandin et al., 2017. J. Exp. Med. jem.rupress.org/cgi/doi/10.1084/jem.20170633

Related Stories

Barrier to autoimmune disease may open door to HIV, study suggests

July 11, 2017
Researchers from the University of Colorado School of Medicine have discovered that a process that protects the body from autoimmune disease also prevents the immune system from generating antibodies that can neutralize the ...

B cells use mechanical forces to pull antigens from other cell surfaces

January 12, 2017
Francis Crick Institute scientists have discovered that immune cells called B cells use mechanical forces to physically pull antigens such as viruses or toxins from the surfaces of other cells.

Discovering the early age immune response in foals

June 28, 2017
Researchers at the College of Veterinary Medicine have discovered a new method to measure tiny amounts of antibodies in foals, a finding described in the May 16 issue of PLOS ONE.

Lamprey-derived antibody specifically recognizes human plasma cells

March 17, 2016
Antibody-secreting plasma cells arise from B cell precursors and are essential for adaptive immune responses against invading pathogens. Plasma cell dysfunction is associated with autoimmune and neoplastic disorders, including ...

How Staph infections elude the immune system

October 27, 2014
A potentially lethal bacterium protects itself by causing immune tunnel vision, according to a study from scientists at The University of Chicago published in The Journal of Experimental Medicine. By tricking the immune system ...

Researchers find key mechanism to control antibody production

April 28, 2017
A research team from iMM Lisboa led by Luís Graça has found a cellular mechanism that underlies the development of autoimmune diseases.

Recommended for you

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

Gene mutation found to cause macrocephaly and intellectual deficits

November 13, 2018
The absence of one copy of a single gene in the brain causes a rare, as-yet-unnamed neurological disorder, according to new research that builds on decades of work by a University at Buffalo biochemist and his colleagues.

Can scientists change mucus to make it easier to clear, limiting harm to lungs?

November 12, 2018
For healthy people, mucus is our friend. It traps potential pathogens so our airways can dispatch nasty bugs before they cause harm to our lungs. But for people with conditions such as cystic fibrosis (CF) and chronic obstructive ...

Mutations, CRISPR, and the biology behind movement disorders

November 12, 2018
Scientists at the RIKEN Center for Brain Science (CBS) in Japan have discovered how mutations related to a group of movement disorders produce their effects. Published in Proceedings of the National Academy of Sciences, the ...

Researchers explain how your muscles form

November 12, 2018
All vertebrates need muscles to function; they are the most abundant tissue in the human body and are integral to movement.

Salmonella found to be resistant to different classes of antibiotics

November 12, 2018
Brazil's Ministry of Health received reports of 11,524 outbreaks of foodborne diseases between 2000 and 2015, with 219,909 individuals falling sick and 167 dying from such diseases. Bacteria caused most outbreaks of such ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

betterexists
not rated yet Jul 24, 2017
CANDIDATE For NOBE PRIZE?
Transfer War-monger Obama's Nobel Peace Prize to These Wizards !

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.