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Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions. | LitMetric

Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions.

J Cell Biol

Department of Biochemistry, Children's Hospital; Department of Electron Microscopy, Center for Molecular Neurobiology; and Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany

Published: January 2015

Antigen processing and presentation and cytotoxic targeting depend on the activities of several lysosomal enzymes that require mannose 6-phosphate (M6P) sorting signals for efficient intracellular transport and localization. In this paper, we show that mice deficient in the formation of M6P residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. The targeting of lysosomal and granular enzymes lacking M6P residues is less affected in dendritic cells and T cells and sufficient for maintenance of degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin levels and antibody responses to vaccination in patients. Our data demonstrate the critical role of M6P-dependent transport routes for B cell functions in vivo and humoral immunity in mice and human.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298682PMC
http://dx.doi.org/10.1083/jcb.201407077DOI Listing

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