Study shows how protein raises antibody output

Columbus , Ohio Cancer immunologists here have discovered how a protein on the surface of antibody-making immune cells boosts the amount of antibody the cells make.

The protein, called CD86, is present on B lymphocytes, or B cells, which make infection-fighting antibodies.

Researchers have long known that B cells use the protein to stimulate other immune cells known as T lymphocytes, or T cells, when the two have contact early in an immune response. But the protein was thought to cause no change in the B-cell itself during that interaction.

The study by Ohio State University scientists is published in a recent issue of The Journal of Immunology.

The research, conducted in mouse cells, provides important details about how B cells make antibodies in response to infections. Antibodies are proteins that attach to viruses, bacteria and other infectious agents to disable them.

The findings could lead to new ways of boosting the immune response against bacteria that cause pneumonia, a leading killer of people with weakened immunity such as cancer and HIV/AIDS, and of controlling autoimmune diseases.

"Our findings describe a previously unknown signaling pathway in B cells that helps regulate antibody production," says principal investigator Virginia M. Sanders, professor in department of molecular virology, immunology and medical genetics and an OSU Comprehensive Cancer Center researcher.

"The findings show that CD86 actually sends signals into the B cell itself, causing it to make a greater amount of antibody. If this is verified in human cells, they could be clinically important."

B cells begin making antibodies after they detect bits of bacteria, viruses or cancer cells in the body. But first the cells must be activated by contact with T cells in lymph nodes. During that interaction, CD86 proteins on the B cells fit like a key into a protein on the T cells called CD28.

If these and other proteins on the two cells also fit together properly, the T cell releases a substance that causes the B cell to proliferate and churn out antibodies against the antigen.

But there was no indication that the interaction between the CD86 protein and a T cell had any influence on the B cell itself.

Earlier work by Sanders and her laboratory, however, strongly suggest the CD86 protein did alter the behavior of the B cell. She and her research team showed that B cells produce much more antibody when CD86 interacts with its T-cell protein than occurs when that interaction is missing.

For this study, Sanders and Kin used two groups of laboratory-grown mouse B cells, which are easier to grow than human B cells.

Then they stimulated one group of B cells with all the signals provided by T cells, including the interaction of CD86 and its T-cell protein. The second group of B cells received all the T-cell signals, except the one for CD86.

The researchers then compared the two groups for changes in antibody levels and changes in the signaling molecules associated with antibody production inside the B cells. This enabled the scientists to trace the chemical changes that begin with CD86 and run through the B cell and the making of antibodies.

"We showed for the first time what signaling molecules are activated inside B cells when CD86 is stimulated," says first author Nicholas W. Kin, a graduate research associate in Sanders' laboratory. "We also found that the signals converge on a protein that controls antibody production.

"This is another piece in the complex puzzle of how the immune system works and how it might be manipulated to fight cancer and autoimmune diseases," Kin adds.

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Funding from the National Institute for Allergies and Infectious Diseases supported this research.

Contact: Darrell E. Ward, Medical Center Communications, 614-293-3737, or Darrell.Ward@osumc.edu


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