The discovery of the role of the CD98hc protein may help find new therapy targets for diseases such as multiple myeloma that are caused by unchecked B cells growth.
Scientists have known for nearly 25 years that CD98hc, common to all vertebrates, probably played a role in their adaptive immune system, but it wasn known how this protein functioned.
"This protein was used as a marker of activation because it was found in low levels on resting lymphocytes," said first author Joseph Cantor from the University of California, San Diego School of Medicine.
"But when B or T lymphocytes were stimulated by antigens - for instance, to protect the body against bacteria - levels of CD98hc went up 20 fold."
The researchers generated a mouse model lacking the CD98hc protein in B-lymphocytes. When vaccinated, these mice were unable to mount a normal antibody response to the pathogen. This was the first clue to the researchers of the proteins importance, Cantor said.
"In purifying B lymphocytes without the CD98hc protein, we discovered that the lymphocytes couldn divide rapidly," he said, adding that this proved the protein was essential to expanding the number of immune cells, a necessary step in the immune response.
The researchers speculated that by blocking the CD98hc protein they could stop the unchecked growth of B lymphocyte cells that can result in cancer or block misdirected B cell attacks that can cause certain autoimmune diseases.
The CD98hc protein functions in cells by helping to transmit integrin signals, as well as transporting amino acids - the building blocks of proteins - into the cell. But the researchers didn know which, if either, of these functions was related to the proteins role in the rapid division of immune cells.
By replacing normal CD98hc in B cells with a version that lacked one or the other of these two functions, they discovered that the integrin-binding domain of this protein is required, but the amino acid transport function is dispensable for B cell proliferation.
"CD98hc interacts with certain integrin subunits to prompt signaling events that control cell migration, survival and proliferation. Our study shows that the rapid proliferation of B cells, necessary for the body to fight infection, is aided by the CD98hc proteins support of integrin signaling," Cantor said.
The study is published online on Sunday in advance of print in the journal Nature Immunology.
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