Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Autophagy has emerged as a critical homeostatic mechanism in T lymphocytes, influencing proliferation and differentiation. Autophagy in B cells has been less studied, but genetic deficiency causes impairment of early and late developmental stagesTo explore the role of autophagy in the pathogenesis of human and murine lupus, a disease in which B cells are critical effectors of pathology.Autophagy was assessed using multiple techniques in NZB/W and control mice, and in patients with systemic lupus erythematosus (SLE) compared to healthy controls. We evaluated the phenotype of the B cell compartment in Vav-Atg7(-/-) mice in vivo, and examined human and murine plasmablast formation following inhibition of autophagy.We found activation of autophagy in early developmental and transitional stages of B cell development in a lupus mouse model even before disease onset, and which progressively increased with age. In human disease, again autophagy was activated compared with healthy controls, principally in naïve B cells. B cells isolated from Vav-Atg7(F/F) mice failed to effectively differentiate into plasma cells following stimulation in vitro. Similarly, human B cells stimulated in the presence of autophagy inhibition did not differentiate into plasmablasts.Our data suggest activation of autophagy is a mechanism for survival of autoreactive B cells, and also demonstrate that it is required for plasmablast differentiation, processes that induce significant cellular stress. The implication of autophagy in two major pathogenic pathways in SLE suggests the potential to use inhibition of autophagy as a novel treatment target in this frequently severe autoimmune disease.

Original publication

DOI

10.1136/annrheumdis-2013-204343

Type

Journal article

Journal

Annals of the rheumatic diseases

Publication Date

05/2015

Volume

74

Pages

912 - 920

Addresses

Medical and Molecular Genetics and Division of Immunology, Infection, and Inflammatory Disease, King's College London, London, UK.

Keywords

B-Lymphocytes, Plasma Cells, Animals, Humans, Mice, Lupus Erythematosus, Systemic, Disease Models, Animal, Case-Control Studies, Lymphocyte Activation, Cell Differentiation, Adult, Autophagy, Female, Male, Precursor Cells, B-Lymphoid