**Apoptosis and Pathology**

46 Apoptosis and Medicine

Wolff, J., (1986), The Law of Bone Remodeling, *Springer (Trans. Maquet, P., Furlong, R.)*

**Chapter 3** 

© 2012 Hirabayashi, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 Hirabayashi, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Cell Death and Anti-DNA Antibodies** 

Autoantibodies are characteristic features of autoimmune diseases (Table 1). In organ or tissue-specific autoimmune diseases, autoantibodies against cell-surface molecules are usually observed. These antibodies (Abs) stimulate or damage the target cells and cause organ- or tissue-specific diseases. In systemic autoimmune diseases, in addition to anti-cellsurface molecule Abs, Abs against intracellular molecules are frequently observed although B cell tolerance to intracellular molecules is strictly enforced in normal subjects. Some indicate high disease specificity with a high incidence rate. Therefore, such Abs may be closely associated with development of the disease as well as with disease activity. However, it is not known how or why Abs against intracellular molecules are generated.

**2. Role of cell death in the generation of anti-intracellular molecule** 

Cell death, including apoptosis and necrosis, represents a possible source of exposure of intracellular molecules outside the cell. For example, low – intermediate doses (< 35 mJ/cm2) of ultraviolet B (UVB) induce apoptosis of keratinocytes, resulting in translocation of native DNA, Ku, and Sm to the cytoplasmic membrane, while a high dose (80 mJ/cm2) of UVB induces necrosis, resulting in discharge of all of the cell compartments [1]. Intracellular molecules are exposed on the surface blebs of apoptotic cells (apoptotic blebs) [2]. Apoptotic blebs contain fragmented endoplasmic reticulum (ER), ribosomes, ribonucleoprotein, nucleosomal DNA, Ro, La, small nuclear ribonucleoproteins, etc. Autoantigens receive various epigenetic modifications (acetylation, methylation, phosphorylation, dephosphorylation, ADP-ribosylation, ubiquitination, oxidation, transglutamination, citrullination, SUMOylation, etc) during apoptotic cell death [3]. In the case of cytotoxic granule-mediated cell death, granzymes plays an important role in cleavage of autoantigens [4]. These epigenetic modifications may alter preexisting epitopes, expose cryptic epitopes,

Additional information is available at the end of the chapter

Yasuhiko Hirabayashi

http://dx.doi.org/10.5772/48343

**1. Introduction** 

**antibodies** 
