Figure 1.

Effect of Atg5 deficiency on plasma cell differentiation and Ab immunity. In differentiating plasma cells, autophagy limits the expansion of the endoplasmic reticulum (ER), providing the first physiological case of mammalian ER-phagy. As a result, Atg5^−/− plasma cells show more abundant ER than wild type counterparts and more intense ER stress signaling (including higher expression of the essential plasma cell transcription factor, XBP-1), which in turn enhances the expression of the key plasma cell transcriptional regulator PRDM1/Blimp-1 and of immunoglobulins (Ig). Hence, despite increased Ig production, autophagy-deficient plasma cells have less ATP and live a shorter life, yielding defective Ab responses in vivo.