Complement factor H modulates splenic B cell development and limits autoantibody production
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-07-11
Date Acceptance
2019-06-27
Citation
Frontiers in Immunology, 2019, 10, pp.1-12
ISSN
1664-3224
Publisher
Frontiers Media
Start Page
1
End Page
12
Journal / Book Title
Frontiers in Immunology
Volume
10
Copyright Statement
© 2019 Kiss, Ozsvár-Kozma, Porsch, Göderle, Papac-Miličević, Bartolini-Gritti, Tsiantoulas, Pickering and Binder. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000475417400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
212252/Z/18/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
complement factor H
complement
autoimmunity
B cell development
B cell receptor signaling
OXIDATION-SPECIFIC EPITOPES
GLOMERULONEPHRITIS
RECEPTORS
MICE
DNA
IMMUNOLOGY
ACTIVATION
SELECTION
DISEASE
SURFACE
Publication Status
Published
Article Number
ARTN 1607
Date Publish Online
2019-07-11