A role for the unfolded protein response in optimizing antibody secretion.

Terminal differentiation of B lymphocytes into antibody(Ab)-secreting plasma cells is marked by a sharp rise in immunoglobulin (Ig) biosynthesis that increases demand on the protein folding capacity of the endoplasmic reticulum (ER). The unfolded protein response pathway (UPR) allows cells to respond to challenging conditions within the ER, in part by the activities of the XBP1 and ATF6alpha/beta transcription factors. The UPR is activated in differentiating B cells, and XBP1 is required for the generation of Ab-secreting plasma cells.

Activation of an unfolded protein response during differentiation of antibody-secreting B cells.

The unfolded protein response pathway (UPR) is believed to detect and compensate for excessive protein accumulation in the endoplasmic reticulum (ER). The UPR can be induced by pharmacological agents that perturb ER functions, but may also occur during cellular developmental processes such as the transition of B-lymphocytes into antibody-secreting plasma cells. Here we show that major UPR components are activated in B cells stimulated to secrete antibody.