Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability

Chaperone proteins are thought to promote the correct folding and assembly of newly synthesized proteins and to facilitate restoration of the folded s tate under environmental conditions that favour protein denaturation. They are among the most ubiquitous and highly conserved of all proteins. The euk aryotic endoplasmic reticulum (ER) chaperone gp96 in particular has long be en thought to be indispensable for cell survival. Here we report that a scr een for genes required for the immune response to bacterial endotoxins has identified a B-cell line deficient in gp96. Absence of gp96 is compatible w ith cellular survival even under stress conditions and causes a defect in t he formation of only a small subset of cell surface receptors. Toll-like re ceptors are retained intracellularly in the absence of gp96, explaining the unresponsiveness of the mutant to microbial stimuli.