Skip to main content

Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2.

Publication ,  Journal Article
Chen, Z; Koralov, SB; Kelsoe, G
Published in: J Exp Med
November 6, 2000

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

November 6, 2000

Volume

192

Issue

9

Start / End Page

1339 / 1352

Location

United States

Related Subject Headings

  • Splenomegaly
  • Spleen
  • Receptors, Complement 3d
  • Receptors, Complement 3b
  • Mice, Knockout
  • Mice, Inbred Strains
  • Mice
  • Male
  • Lymphocyte Activation
  • Lupus Erythematosus, Systemic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, Z., Koralov, S. B., & Kelsoe, G. (2000). Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2. J Exp Med, 192(9), 1339–1352. https://doi.org/10.1084/jem.192.9.1339
Chen, Z., S. B. Koralov, and G. Kelsoe. “Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2.J Exp Med 192, no. 9 (November 6, 2000): 1339–52. https://doi.org/10.1084/jem.192.9.1339.
Chen, Z., et al. “Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2.J Exp Med, vol. 192, no. 9, Nov. 2000, pp. 1339–52. Pubmed, doi:10.1084/jem.192.9.1339.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

November 6, 2000

Volume

192

Issue

9

Start / End Page

1339 / 1352

Location

United States

Related Subject Headings

  • Splenomegaly
  • Spleen
  • Receptors, Complement 3d
  • Receptors, Complement 3b
  • Mice, Knockout
  • Mice, Inbred Strains
  • Mice
  • Male
  • Lymphocyte Activation
  • Lupus Erythematosus, Systemic