Retinoic acid-induced IgG production in TLR-activated human primary B cells involves ULK1-mediated autophagy.

Retinoic acid-induced IgG production in TLR-activated human primary B cells involves ULK1-mediated autophagy.
Autophagy. 2015 Mar 6;:0
Authors: Eriksen AB, Torgersen ML, Holm KL, Abrahamsen G, Spurkland A, Moskaug JØ, Simonsen A, Blomhoff HK
Abstract
In the present study we have established a vital role of autophagy in retinoic acid (RA)-induced differentiation of toll-like receptor (TLR)-stimulated human B cells into Ig-secreting cells. Thus, RA enhanced autophagy in TLR9- and CD180-stimulated peripheral blood B cells, as revealed by increased levels of the autophagosomal marker LC3B-II, enhanced colocalization between LC3B and the lysosomal marker Lyso-ID, by a larger percentage of cells with more than 5 characteristic LC3B puncta, and by the concomitant reduction in the level of SQSTM1/p62. Furthermore, RA induced expression of the autophagy-inducing protein ULK1 at the transcriptional level, in a process that required the retinoic acid receptor RAR. By inhibiting autophagy with specific inhibitors or by knocking down ULK1 by siRNA, the RA-stimulated IgG production in TLR9- and CD180-mediated cells was markedly reduced. We propose that the identified prominent role of autophagy in RA-mediated IgG-production in normal human B cells provides a novel mechanism whereby vitamin A exerts its important functions in the immune system.
PMID: 25749095 [PubMed - as supplied by publisher]

Source: Autophagy - March 6, 2015 Category: Cytology Authors: Eriksen AB, Torgersen ML, Holm KL, Abrahamsen G, Spurkland A, Moskaug JØ, Simonsen A, Blomhoff HK Tags: Autophagy Source Type: research