Designer Antibodies: Cell Repair Mechanism Promises Immune System Control

October 09, 1997

Immune system B cells are an inventive little army. When challenged by antigens - proteins produced by invaders such as bacteria - they proliferate and secrete other proteins called immunoglobulins or antibodies. The molecular structure of these antibodies is a perfect fit, a receptor that locks onto and disarms the enemy.

Immunologists know there is genetic machinery that generates countless kinds of antibodies in immature B cells developing in the bone marrow, but up to now, they believed the design process was random and independent of antigen's presence or influence. And they thought that once B cells matured, they lost their ability to recombine their genetic material and produce new and different antibodies.

Not so, says Dr. Garnett Kelsoe, professor of microbiology and immunology at the University of Maryland School of Medicine. Mature B cells can reactivate the molecular machinery that makes new genes, which in turn design novel antibody molecules. What's more, they can do it outside the bone marrow, in peripheral lymphoid tissues such as the spleen and lymph nodes. Even more significant is the fact that their renewed recombination of the B cells' genetic material is antigen-driven. "The antigen in effect instructs failing B cell to make a new, antigen-specific receptor," Kelsoe said. In other words, the intruder itself hands the defending army a blueprint for repairing ineffective weapons against it.

"At least in theory, this means we could expand lymphocyte repertoires to meet a patient's needs," he said. For example, it should be possible to reconstitute more quickly the damaged immune system of a cancer patient whose bone marrow has been irradiated.

Kelsoe and colleagues report on their findings in the October 10 issue of the journal Science.

The University of Maryland School of Medicine researchers, including Kelsoe, Shuhua Han, Biao Zheng, and Michiko Shimoda, and collaborators Stacey R. Dillon and Mark S. Schlissel at Johns Hopkins University School of Medicine, immunized mice with antigen, jumpstarting an immune reaction. Lymphocytes began proliferating in the spleen, growing into collections of active B and T cells known as germinal centers. In the germinal centers, where rapid mutation produces many B cells destined to fail and die, the recombination enzymes were turned back on in failing B cells, enzymes were turned back on, causing the cells' genetic material to recombine, generating new antibodies that were a perfect fit for the antigen threatening them.

"We now know that the recombination enzymes are being expressed again in mature B cells; we know that the genes are being rearranged, and we know that this mechanism actually is responding to antigen exposure," Kelsoe said.

"This appears to be a rescue mechanism for cells that have been damaged by mutation," he suggested. "The germinal center is a Darwinian microcosm, and every potential soldier is an investment worth protecting."

Kelsoe and colleagues' research was funded in part by the National Institutes of Health, the Leukemia Society of America, the Arthritis Society, the Jeanne M. and Joseph P. Sullivan Foundation and the Santa Fe Institute.

University of Maryland School of Medicine

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.