The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

Abstract

A classical function of C1q is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elicited when C1q binds some other ligands. Besides complement activation, C1q also regulates cell differentiation, adhesion, migration, activation and survival. C1q deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of C1q, its expression, and classical and regulatory functions. Cellular & Molecular Immunology. 2008;5(1):9-21.

Molecular Mechanisms for Synchronized Transcription of Three Complement C1q Subunit Genes in Dendritic Cells and Macrophages

“…The reduced C1q levels could attribute partly to inflammatory consumption and anti-C1q autoantibodies (27,28). However, C1q expression is also versatile, which is affected by diverse microbial stimuli, cytokines, hormones, and drugs (19). Second, C1q production is largely restricted to DCs and macrophages, but the transcription mechanisms are unknown.…”

“…In addition to these ligand-dependent C1q functions, which can involve complement activation and phagocytosis, ligandindependent C1q functions have also been reported (19). For example, both soluble and solid phase C1q were shown to affect monocyte differentiation into DCs so that these cells were less immunostimulatory or more tolerogenic (20,21).…”

“…Without known gene defect, acquired C1q deficiency can occur (25,26). C1q consumption by immune complexes and anti-C1q autoantibodies are likely causes (27,28 affect C1q production (19), which can contribute to the decline of C1q levels in SLE patients. C1q is a delicate 18-subunit assembly in 1:1:1 ratio from three types of subunits (29).…”

Gene Expression Changes in Multiple Sclerosis Relapse Suggest Activation of T and Non-T Cells

“…C1QC also was decreased, but with a lower significance level. The C1Q protein is a complex of C1QA, C1QB and C1QC, and is synthesized in macrophages or dendritic cells and secreted into the serum (11). The amount of C1Q in stable disease was 78.7 ± 4.3 μg/mL with an increase of 0.5 ± 6.8 in relapse (not significant, n = 20).…”

“…Dendrogram constructed using BRB ArrayTools with centered correlation and average linkage. The branch labels give the experiment number (1)(2)(3)(4)(5), the subject number (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), clinical status, treatment, and gender. The samples from the first two experiments formed large clusters.…”