G alpha q-containing G proteins regulate B cell selection and survival and are required to prevent B cell-dependent autoimmunity.

The Journal of Experimental Medicine
Ravi S MisraFrances E Lund

Abstract

Survival of mature B cells is regulated by B cell receptor and BAFFR-dependent signals. We show that B cells from mice lacking the G(alphaq) subunit of trimeric G proteins (Gnaq(-/-) mice) have an intrinsic survival advantage over normal B cells, even in the absence of BAFF. Gnaq(-/-) B cells develop normally in the bone marrow but inappropriately survive peripheral tolerance checkpoints, leading to the accumulation of transitional, marginal zone, and follicular B cells, many of which are autoreactive. Gnaq(-/-) chimeric mice rapidly develop arthritis as well as other manifestations of systemic autoimmune disease. Importantly, we demonstrate that the development of the autoreactive B cell compartment is the result of an intrinsic defect in Gnaq(-/-) B cells, resulting in the aberrant activation of the prosurvival factor Akt. Together, these data show for the first time that signaling through trimeric G proteins is critically important for maintaining control of peripheral B cell tolerance induction and repressing autoimmunity.

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Citations

Apr 9, 2013·Archivum Immunologiae Et Therapiae Experimentalis·Yantang WangGuixiu Shi
Oct 17, 2012·The Journal of Biological Chemistry·Prabha ChandrasekaranSundararajan Venkatesan
Jun 25, 2014·Immunology and Cell Biology·Dashan WangGuixiu Shi
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Mar 4, 2015·Immunology and Cell Biology·Yuan LiuGuixiu Shi
Feb 16, 2017·Mediators of Inflammation·Dashan WangGuixiu Shi
Sep 19, 2019·Nature Communications·Zhaoming LiMingzhi Zhang
Jun 26, 2018·International Immunology·Shuyin LiJi-Yang Wang
Aug 24, 2017·Scientific Reports·Magdalena KrochmalJoachim Jankowski
Aug 2, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cedric BoularanJohn H Kehrl
Mar 12, 2019·Communications Biology·Subhayan ChattopadhyayAsta Försti
Aug 26, 2018·Arthritis Research & Therapy·Yan HeGuixiu Shi
Dec 4, 2020·FEBS Letters·Nadia Arang, J Silvio Gutkind
Feb 9, 2021·Frontiers in Immunology·Soumyaroop BhattacharyaThomas J Mariani

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Methods Mentioned

BETA
flow cytometry
FACS
fluorescence microscopy
ELISA
Infrared Imaging

Software Mentioned

AxioVision
Visionworks LS
NIS Elements
AxioVision Rel
NIS Elements Acquisition
Canvas

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