Study Has Implications for Vaccine Design and Autoimmune Diseases

A report in Nature November 17 by Yale School of Medicine researchers emphasizes which cells are important in mounting an antibody response to invading microbes.

Ruslan Medzhitov, professor in the Section of Immunobiology, Howard Hughes Medical Institute investigator, and lead author of the study, said that in order to elicit good antibody responses, it now appears that successful vaccines must incorporate activation ligands for the Toll like receptors (TLRs) of both B cells and dendritic cells.

One way the immune system combats infection is with antibodies, targeting molecules that are secreted by B cells, a type of white blood cell. To produce antibodies, B cells interact with other immune system cells, helper T cells, which are activated by dendritic cells that have detected microbial infection through their Toll like receptors. Although B cells have their own TLRs, until this study, their role was a mystery.

Chandrashekhar Pasare, an associate research scientist in Medzhitov’s laboratory, examined the importance of the B cell TLRs and dendritic cells for sensing microbes. They found the expected antibody production by B cells from dendritic cell activated T cells. “However, we found that B cells also needed to sense microbes via their own TLRs for optimal production of antibodies,” Pasare said.

“Until now, it was thought that B cell activation was controlled by the helper T cells, and helper T cells were in turn controlled by dendritic cells,” Medzhitov said. “The emphasis of the field was on the dendritic cell recognizing the microbes via their TLRs and not the lymphocytes.”

The researchers said the results of this study may also shed light on both the pathogenesis and treatment of autoimmune diseases mediated by B cells, such as lupus or myasthenia gravis.