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J Cell Sci. 2019 Nov 28. pii: jcs.235192. doi: 10.1242/jcs.235192. [Epub ahead of print]

B cells rapidly target antigen and surface-derived MHCII into peripheral degradative compartments.

Author information

1
Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, Finland.
2
Turku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland.
3
Institute of Biotechnology, Electron Microscopy Unit, University of Helsinki, Finland.
4
Facility for Imaging by Light Microscopy (FILM), National Heart and Lung Institute, Imperial College London, UK.
5
Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, Finland pieta.mattila@utu.fi.

Abstract

In order to mount high-affinity antibody responses, B cells internalise specific antigens and process them into peptides loaded onto MHCII for presentation to TH cells. While the biochemical principles of antigen processing and MHCII loading have been well dissected, how the endosomal vesicle system is wired to enable these specific functions remains much less studied. Here, we performed a systematic microscopy-based analysis of antigen trafficking in B cells to reveal its route to the MHCII peptide-loading compartment (MIIC). Surprisingly, we detected fast targeting of internalised antigen into peripheral acidic compartments that possessed the hallmarks of MIIC and also showed degradative capacity. In these vesicles, internalised antigen converged rapidly with membrane-derived MHCII and partially overlapped with Cathepsin-S and H2-M, both required for peptide loading. These early compartments appeared heterogenous and atypical as they contained a mixture of both early and late markers, indicating specialized endosomal route. Together, our data suggests that, in addition to previously-reported perinuclear late endosomal MIICs, antigen processing and peptide loading could start already in these specialized early peripheral acidic vesicles (eMIIC) to support fast peptide-MHCII presentation.

KEYWORDS:

Adaptive immune system; Antigen processing; B cell receptor; B cells; BCR; Endosomes; MHCII; Peptide-loading; Vesicle traffic

PMID:
31780582
DOI:
10.1242/jcs.235192

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