Autoantibodies: Focus on anti-DNA antibodies

Abstract

Ever since the days of Ehrlich and the birth of humoral immunity, self-reactivity or 'horror autotoxicus' as referred to by Paul Ehrlich, has been of great concern. For instance, in patients with the autoimmune disease systemic lupus erythematosus (SLE), anti-nuclear and anti-DNA antibodies have been recognized for many years. Despite this, the exact mechanism as to how the immune system fails to protect the individual and allows these autoantibodies to develop in this and other systemic autoimmune diseases remains uncertain. So how can we explain their presence? Evidence suggests that B cells expressing autoreactive antibodies do not normally arise but rather undergo negative selection as they develop. In light of this, it might seem contradictory that not all autoreactive B cell clones are eliminated, although this may not even be the intention since autoantibodies are also found in healthy individuals and may even protect from autoimmunity. Here, we will discuss autoantibodies, in particular those recognizing DNA, with regard to their reactivity and their potentially pathogenic or protective properties.

Figure 1

General structure of an IgG antibody. This consists of an identical pair of Ig HCs and LCs each containing a variable and constant region.

Figure 2

Schematic picture of HC and LC CDRs and FWRs. The HC and LC variable regions are encoded by the recombined V(D)J gene segments. The relative positions of the CDR1-3 and the FWR1-4 are indicated.

Figure 3

Molecular model of the interaction between an anti-DNA antibody and DNA. According to the proposed model, the HC-CDR1 and HC-CDR2 extend into the major groove of DNA whereas the HC-CDR3 straddles one of the phosphate backbones. The loop of the HC-FWR3 is positioned such that it contributes to contacts within the minor groove. The LC binds primarily through CDR1, which reaches into the minor groove. Adapted from reference .