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B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8− dendritic cells require the intramembrane endopeptidase SPPL2A

Overview of attention for article published in The Journal of Experimental Medicine, December 2012
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Title
B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8− dendritic cells require the intramembrane endopeptidase SPPL2A
Published in
The Journal of Experimental Medicine, December 2012
DOI 10.1084/jem.20121076
Pubmed ID
Authors

Hannes Bergmann, Mehmet Yabas, Alanna Short, Lisa Miosge, Nadine Barthel, Charis E. Teh, Carla M. Roots, Katherine R. Bull, Yogesh Jeelall, Keisuke Horikawa, Belinda Whittle, Bhavani Balakishnan, Geoff Sjollema, Edward M. Bertram, Fabienne Mackay, Andrew J. Rimmer, Richard J. Cornall, Matthew A. Field, T. Daniel Andrews, Christopher C. Goodnow, Anselm Enders

Abstract

Druggable proteins required for B lymphocyte survival and immune responses are an emerging source of new treatments for autoimmunity and lymphoid malignancy. In this study, we show that mice with an inactivating mutation in the intramembrane protease signal peptide peptidase-like 2A (SPPL2A) unexpectedly exhibit profound humoral immunodeficiency and lack mature B cell subsets, mirroring deficiency of the cytokine B cell-activating factor (BAFF). Accumulation of Sppl2a-deficient B cells was rescued by overexpression of the BAFF-induced survival protein B cell lymphoma 2 (BCL2) but not BAFF and was distinguished by low surface BAFF receptor and IgM and IgD B cell receptors. CD8-negative dendritic cells were also greatly decreased. SPPL2A deficiency blocked the proteolytic processing of CD74 MHC II invariant chain in both cell types, causing dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 endosomal retention and processing. The findings illuminate an important role for the final step in the CD74-MHC II pathway and a new target for protease inhibitor treatment of B cell diseases.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 91 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Germany 1 1%
Italy 1 1%
Canada 1 1%
Unknown 87 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 32 35%
Student > Ph. D. Student 20 22%
Student > Bachelor 8 9%
Professor 7 8%
Student > Master 6 7%
Other 9 10%
Unknown 9 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 40 44%
Biochemistry, Genetics and Molecular Biology 14 15%
Medicine and Dentistry 12 13%
Immunology and Microbiology 10 11%
Business, Management and Accounting 1 1%
Other 4 4%
Unknown 10 11%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 February 2013.
All research outputs
#17,313,103
of 25,411,814 outputs
Outputs from The Journal of Experimental Medicine
#10,883
of 11,610 outputs
Outputs of similar age
#193,945
of 289,282 outputs
Outputs of similar age from The Journal of Experimental Medicine
#31
of 41 outputs
Altmetric has tracked 25,411,814 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 11,610 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.4. This one is in the 2nd percentile – i.e., 2% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 289,282 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.