Many antibodies with millions of different fine specificities are produced in humoral immune responses by B lymphocytes and their progeny, as part of the adaptive immune system, and we will describe antibodies and B cell responses in detail in later chapters. However, there are subsets of B cells that produce antibodies with only a limited number of specificities without overt exposure to foreign antigens, and these are called natural antibodies. As is typical for other components of innate immunity, natural antibodies are already present before infections, and they recognize common molecular patterns on microbes or stressed and dying cells. Natural antibodies are usually specific for carbohydrate or lipid molecules but not proteins, and most are IgM antibodies, one of several structural classes of Ig molecules (see Chapter 5). A remarkably large proportion of the natural antibodies in humans and mice are specific for oxidized lipids, including phospholipid head groups such as lyso-phosphatidylcholine and phosphorylcholine, which are found on bacterial membranes and on apoptotic cells but are not exposed on the surface of healthy host cells. Some experimental evidence indicates that the natural antibodies specific for these phospholipids provide protection against bacterial infections and facilitate the phagocytosis of apoptotic cells. The anti-ABO blood
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