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Complement factor H modulates splenic B cell development and limits autoantibody production

Title: Complement factor H modulates splenic B cell development and limits autoantibody production
Authors: Kiss, MG
Ozsvar-Kozma, M
Porsch, F
Goderle, L
Papac-Milicevic, N
Bartolini-Gritti, B
Tsiantoulas, D
Pickering, MC
Binder, CJ
Item 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.
Issue Date: 11-Jul-2019
Date of Acceptance: 27-Jun-2019
URI: http://hdl.handle.net/10044/1/87716
DOI: 10.3389/fimmu.2019.01607
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.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 212252/Z/18/Z
Keywords: 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
B cell development
B cell receptor signaling
autoimmunity
complement
complement factor H
Animals
Autoantibodies
Autoimmunity
B-Lymphocyte Subsets
B-Lymphocytes
Biomarkers
Cell Differentiation
Complement Factor H
Immunophenotyping
Lymphocyte Activation
Mice
Mice, Knockout
Receptors, Antigen, B-Cell
Signal Transduction
Spleen
Spleen
B-Lymphocytes
B-Lymphocyte Subsets
Animals
Mice, Knockout
Mice
Complement Factor H
Receptors, Antigen, B-Cell
Autoantibodies
Immunophenotyping
Lymphocyte Activation
Signal Transduction
Cell Differentiation
Autoimmunity
Biomarkers
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
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN 1607
Online Publication Date: 2019-07-11
Appears in Collections:Department of Immunology and Inflammation



This item is licensed under a Creative Commons License Creative Commons