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Autophagy. 2015;11(3):460-71. doi: 10.1080/15548627.2015.1009797.

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

Author information

1
a Department of Biochemistry ; Institute of Basic Medical Sciences; University of Oslo ; Oslo , Norway.

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.

KEYWORDS:

ATG, autophagy-related; B lymphocytes; BDS, bright detail similarity; CD180; CD180, CD180 molecule; CVID, common variable immune deficiency; ELISA, enzyme-linked immunosorbent assay; IL, interleukin; Ig, immunoglobulin; MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 β; MTOR, mechanistic target of rapamycin (serine/threonine kinase); PAMP, pathogen-associated molecular pattern, PML/RARA, promyelocytic leukemia/ retinoic acid receptor α; RA, all-trans retinoic acid; RAR, retinoic acid receptor; RP105; SQSTM1, sequestosome 1; TLR, toll-like receptor; TLR9; ULK1; ULK1, unc-51 like autophagy activating kinase 1; antibody secretion; autophagy; plasma cell differentiation; retinoic acid

PMID:
25749095
PMCID:
PMC4502696
DOI:
10.1080/15548627.2015.1009797
[Indexed for MEDLINE]
Free PMC Article

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