ArticleThe Journal of experimental medicine2000
Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 162 citations in OpenAlex.
- Divergent roles for complement components C3 and C4 in controllingbioRxiv : the preprint server for biology · 2025Article
- Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies.Journal of leukocyte biology · 2024Review
- Application of a dried blood spot based proteomic and genetic assay for diagnosing hereditary angioedema.Clinical and translational allergy · 2023Article
- Intertwined pathways of complement activation command the pathogenesis of lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Expanding the Role of Complement Therapies: The Case for Lupus Nephritis.Journal of clinical medicine · 2021Review
- Complement C4, Infections, and Autoimmune Diseases.Frontiers in immunology · 2021Review
- Tracing Self-Reactive B Cells in Normal Mice.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Serum immunoglobulin G4 in Sjögren's syndrome: a pilot study.Rheumatology international · 2020Article
- Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies.Pediatric rheumatology online journal · 2019Article
- Complement Factor H Modulates Splenic B Cell Development and Limits Autoantibody Production.Frontiers in immunology · 2019Article
- Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis.Scientific reports · 2017Article
- Clearance Deficiency and Cell Death Pathways: A Model for the Pathogenesis of SLE.Frontiers in immunology · 2016Review
- Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- C4 Deficiency is a predisposing factor for Streptococcus pneumoniae-induced autoantibody production.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus.Disease models & mechanisms · 2014Review
- Autoimmune effector memory T cells: the bad and the good.Immunologic research · 2013Review
- Suppression of Th1 cytokine production by a peptide derived from C4b.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2013Article
- CAWS administration increases the expression of interferon γ and complement factors that lead to severe vasculitis in DBA/2 mice.BMC immunology · 2013Article
- Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner.European journal of immunology · 2013Article
- Identification of altered plasma proteins by proteomic study in valvular heart diseases and the potential clinical significance.PloS one · 2013Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The complement system enhances antibody responses to T-dependent antigens, but paradoxically, deficiencies in C1 and C4 are strongly linked to autoantibody production in humans. In mice, disruption of the C1qa gene also results in spontaneous autoimmunity. Moreover, deficiencies in C4 or complement receptors 1 and 2 (CR1/CR2) lead to reduced selection against autoreactive B cells and impaired humoral responses. These observations suggest that C1 and C4 act through CR1/CR2 to enhance humoral immunity and somehow suppress autoimmunity. Here we report high titers of spontaneous antinuclear antibody (ANA) in C4(-/)- mice. This systemic lupus erythematosus-like autoimmunity is highly penetrant; by 10 mo of age, all C4(-)(/)- females and most males produced ANA. In contrast, titers and frequencies of ANA in Cr2(-)(/)- mice, which are deficient in CR1 and CR2, never rose significantly above those in normal controls. Glomerular deposition of immune complexes (ICs), glomerulonephritis, and splenomegaly were observed in C4(-)(/)- but not Cr2(-)(/)- mice. C4(-)(/)-, but not Cr2(-)(/)-, mice accumulate activated T and B cells. Clearance of circulating ICs is impaired in preautoimmune C4(-)(/)-, but not Cr2(-)(/)-, mice. C4 deficiency causes spontaneous, lupus-like autoimmunity through a mechanism that is independent of CR1/CR2.
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Registered trials
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