Controlapoptotic

Fig. 17.1. Autoantigens cluster in unique apoptotic subcellular structures. Lupus autoantigens are not restricted to any specific subcellular compartment in normal cells. However, in cells dying by apoptosis induced by numerous different apoptotic stimuli, they become clustered and concentrated within small surface blebs and apoptotic bodies. In addition, phosphatidylserine, which is normally restricted to the inner surface of the plasma membrane bilayer, becomes rapidly redistributed early in apoptosis and appears at the external membrane surface. Interestingly, surface blebs of apoptotic keratinocytes bind C1q, whose collagen-like domains are the frequent (~47%) target of a high titer antibody response in patients with systemic lupus erythematosus. PS, phosphatidylserine

SMALL BLEBS:

Ro (52 kDa) Ribosomal P

SMALL BLEBS:

Ro (52 kDa) Ribosomal P

PS-protein complexes

PS-protein complexes

Ro/SSA (60 kDa), La/SSB, snRNPs, Ku, and poly(ADP-ribose)polymerase (normally diffusely distributed throughout the nucleus) became concentrated as a rim around the condensing chromatin and apoptotic bodies. In addition to the enrichment of lupus autoantigens within apoptotic surface blebs, anionic phospholipids, particularly phosphatidylserine (PS), are also found concentrated at the surface of these structures (Casciola-Rosen et al. 1996, Fadok et al. 1992, Price et al. 1996). The humoral response to anionic phospholipids in lupus seems to recognize complexes of the phospholipid and one of several PS-binding proteins, for example, 02-glycopro-tein 1 or annexin V. Recent studies have also demonstrated that anti-DNA antibodies recognize their cognate antigens at the surface of apoptotic cells (Cocca et al. 2001).

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