Scientists have identified a protein that plays a major role in the division and replication of the immune cells called B lymphocytes.
B lymphocytes' rapid generation is critical to the body's antibody defense mechanism.
Researchers at the University of California, San Diego School of Medicine highlight the fact that when B cells grow unchecked, it can lead to immune cell cancers such as multiple myeloma or, when they grow to attack the wrong targets, to autoimmune disease.
They say that the discovery of the role played by the CD98hc protein, it may now be possible to develop new therapy targets for such diseases.
Dr. Mark H. Ginsberg, a professor of medicine in whose laboratory the study was conducted, said that his team's work describes why CD98hc is essential in order for B lymphocytes to transition into antibody-secreting cells.
He further says that the study also describes how this relates to the protein's role in the signaling ability of integrins, a large family of adhesion molecules that transfer information between the inside and outside of a cell.
Dr. Joseph Cantor, the first author of the study, points out that 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't 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 Cantor. "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," Nature magazine quoted him as saying.
For their study, the researchers generated a mouse model that lacked the CD98hc protein in B lymphocytes.
Upon vaccinating the mice, the researchers observed that the animals were unable to mount a normal antibody response to the pathogen.
Cantor says that that was the first clue to the importance of the protein.
"In purifying B lymphocytes without the CD98hc protein, we discovered that the lymphocytes couldn't divide rapidly," Cantor 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 said that even though the deletion of the protein did not impair early B cell activation, it did inhibit later activation of elements along the signaling pathway that push the cell forward to divide.
"Since B cells can't rapidly divide and replicate without CD98hc, perhaps by blocking this protein we 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," said Ginsberg.
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 it was unclear as to which of these functions was related to the protein's role in the rapid division of immune cells.
During the current study, the researcher replaced normal CD98hc in B cells with a version that lacked one or the other of these two functions.
They found that the integrin-binding domain of the protein was 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 protein's support of integrin signaling," Cantor said.
The study has been published in the online edition of the journal Nature Immunology.