Imperial College London
Alternate

ProfessorMatthewPickering

Faculty of Medicine, Department of Immunology and Inflammation

Centre Director, Professor of Rheumatology
 
 
 
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Contact

 

matthew.pickering Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N12Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kiss:2019:10.3389/fimmu.2019.01607,
author = {Kiss, MG and Ozsvar-Kozma, M and Porsch, F and Goderle, L and Papac-Milicevic, N and Bartolini-Gritti, B and Tsiantoulas, D and Pickering, MC and Binder, CJ},
doi = {10.3389/fimmu.2019.01607},
journal = {Frontiers in Immunology},
pages = {1--12},
title = {Complement factor H modulates splenic B cell development and limits autoantibody production},
url = {http://dx.doi.org/10.3389/fimmu.2019.01607},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Complement factor H (CFH) has a pivotal role in regulating alternative complement activation through its ability to inhibit the cleavage of the central complement component C3, which links innate and humoral immunity. However, insights into the role of CFH in B cell biology are limited. Here, we demonstrate that deficiency of CFH in mice leads to altered splenic B cell development characterized by the accumulation of marginal zone (MZ) B cells. Furthermore, B cells in Cfh−/− mice exhibit enhanced B cell receptor (BCR) signaling as evaluated by increased levels of phosphorylated Bruton's tyrosine kinase (pBTK) and phosphorylated spleen tyrosine kinase (pSYK). We show that enhanced BCR activation is associated with uncontrolled C3 consumption in the spleen and elevated complement receptor 2 (CR2, also known as CD21) levels on the surface of mature splenic B cells. Moreover, aged Cfh−/− mice developed splenomegaly with distorted spleen architecture and spontaneous B cell-dependent autoimmunity characterized by germinal center hyperactivity and a marked increase in anti-double stranded DNA (dsDNA) antibodies. Taken together, our data indicate that CFH, through its function as a complement repressor, acts as a negative regulator of BCR signaling and limits autoimmunity.
AU  - Kiss,MG
AU  - Ozsvar-Kozma,M
AU  - Porsch,F
AU  - Goderle,L
AU  - Papac-Milicevic,N
AU  - Bartolini-Gritti,B
AU  - Tsiantoulas,D
AU  - Pickering,MC
AU  - Binder,CJ
DO  - 10.3389/fimmu.2019.01607
EP  - 12
PY  - 2019///
SN  - 1664-3224
SP  - 1
TI  - Complement factor H modulates splenic B cell development and limits autoantibody production
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2019.01607
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000475417400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2019.01607/full
UR  - http://hdl.handle.net/10044/1/87716
VL  - 10
ER  -
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