Protein A of Staphylococcus aureus (SpA), and presumably other superantigens, induce B lymphocyte apoptosis by targeting conserved sites in B cell receptors, investigators report in the May 5th issue of the Journal of Experimental Medicine.
Superantigens interact with conserved sites in variable regions of B cell receptors, rather than with complementarity determining regions, explain the researchers, who are based at the University of California San Diego in La Jolla. Treatment with SpA leads to a rapid loss of SpA-reactive B cells in the peripheral and central compartments. However, the mechanism by which superantigens affect host immune systems remains unknown.To investigate, the scientists instilled recombinant SpA into the peritoneal cavity of mice. They subsequently observed three phases of apoptotic B cell death, the report indicates. Within 2 hours, surface immunoglobulins were downregulated, as was the B coreceptor CD19.In what the authors call a “decision phase,” mitochondrial transmembrane potential was dissipated. In vitro studies using isolated splenocytes suggest that this phase can be aborted by addition of interleukin-4 or CD40L.However, when the process was allowed to proceed unimpeded, the caspase pathway was induced and DNA fragmentation occurred over the ensuing 4 to 6 days. At the same time, the absolute numbers of B cells were reduced in the spleen, peripheral and mesenteric lymph nodes and Peyer’s patches, as well as in the blood, liver and lung.”This mechanism may explain why staph infections are so common and why many people get them recurrently,” Dr. Silverman proposes in a UCSC press statement.”We should be able to use the same process induced by SpA to treat the disease-causing B cells in autoimmune diseases and cancers like leukemia and lymphoma [and] to make protective vaccines against staph,” he adds.(Source: J Exp Med 2003;197:00-00: www.jem.org/cgi/doi/10.1084/jem.20020552: Reuters Health: May 1, 2003: Oncolink)