Journal of Cell Biology 2015-01-19

Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions.

Takanobu Otomo, Michaela Schweizer, Katrin Kollmann, Valéa Schumacher, Nicole Muschol, Eva Tolosa, Hans-Willi Mittrücker, Thomas Braulke

文献索引：J. Cell Biol. 208(2) , 171-80, (2015)

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摘要

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. © 2015 Otomo et al.