Gene Depletion Blocks B Cell Proliferation

Immunologists have created a valuable research tool by genetically engineering a line of mice to lack the gene for CD98hc, a protein that plays a critical role in the transition of naïve B-lymphocytes into active, antibody secreting cells.

Investigators from the University of California, San Diego (La Jolla, USA) studied the alterations in B cell function induced by depletion of the heavy chain of the CD98 protein (CD98hc). They reported in the March 8, 2009, online edition of the journal Nature Immunology that B cell-specific deletion of CD98hc resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and down regulation of the cell cycle inhibitor p27.

CD98hc has two distinct functions in cells, transmitting of integrin signals and transporting amino acids. By replacing normal CD98hc in B cells with a mutated version that lacked one or the other of these two functions, the investigators found that the integrin-binding domain was required for B cell proliferation, but that the amino acid transport function could be routed through other pathways.

"Since B cells cannot 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 senior author Dr. Mark H. Ginsberg, professor of medicine at the University of California, San Diego.

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