Both systems utilize the antibody homophilicity. in the immune homeostasis and protection against pathogens (16). B1 cells in mice produce natural antibodies (7,8). In human, CD20+CD27+CD43+memory B Morroniside cells were recently identified as murine B1 counterpart (9). Natural antibodies are the important components of the Morroniside therapeutic intravenous immunoglobulin (IVIG) (1012) that is widely used in the therapy of autoimmune and inflammatory diseases (1317). These functions of natural antibodies also indicate diverse roles played by B cells in the immune homeostasis (1822). == The Idiotypic Interactions == Oudin and Jerne are the founders of the idiotype concept (23,24). They discovered that one antibody could recognize another antibody as an individual and unique member of the immune system. The uniqueness of an antibody lies in the variable region of heavy and light chains and has been named idiotype. The idiotype antibody individuality is separated from the antigen-binding site, also determined by unique sequence variability. However, both regions are linked by a unique variability and have a functional relation. Identifying an antigen-binding site also reveals the linked idiotype andvice versa, an idiotope reveals the associated antigen specificity. However, there are important exceptions to this linkage rule: the so-called common idiotopes (IdX) are expressed on antibodies with different antigen specificities (25). Furthermore, antigen-binding site and idiotype site can be identical or overlapping. Studies on the functional interactions of anti-idiotype binding to antibodies have established a classification in the idiotype field. Jerne termed anti-idiotypes that do not interfere with the antigen-binding site as Ab2 and anti-idiotypes that block the antigen binding as Ab2 (26). Ab2 was further differentiated by adding the term Ab2 to describe Ab2 that only partially inhibits antigen binding (27,28). The Ab2 has another unique functional feature. It mimics the antigen by its perfect fit into another antigen-binding site. Ab2 has been used as an antigen to induce a specific immune response (28). Another Morroniside shared idiotype has been discovered in HIV-infected primates (29). This anti-idiotype antibody has been termed as Ab2 (30). In mice, prime antibodies lack the dominant expression of certain shared idiotype, such as the so-called T15 idiotype, that develops weeks after birth without environmental challenge (31,32). Therefore, the T15 dominance can be considered a part of the natural antibody repertoire. The T15 idiotype is also present in primates, including man (33). Perhaps a review of the idiotypic circuits is helpful for the understanding of the biological and immunological properties of the T15 archetypic idiotype. A hallmark of the T15 antibody family is their ability to self bind for producing homophilic complexes (3436). The domain responsible for antibody self-binding (homophilicity) has been described as a region in VH of T15, extending from CDR2 to Fr3 (35,37). Because Rabbit polyclonal to AGPS of their preimmune presence in normal sera, homophilic antibodies are segment of the natural antibody repertoire (33,37). == The Biology and Immunoregulatory Functions of Homophilic Antibodies == The homophilic domain in antibodies was identified, and peptides that can confer the homophilic effect to other antibodies were made (38). Further studies showed that the homophilic domain can be expressed independently from the specificity of the antigen-binding site (39). This suggested that any antibody could be made homophilic by attaching the homophilic domain. In early experiments, a chemical affinity conjugation method Morroniside was introduced to make the homophilic Ig (40); later, recombinant techniques were used to produce a homophilic antibody fusion protein. Human and mouse sera contain antibodies that express the homophilic domain (33), confirming that homophilic antibodies are part of the so-called natural antibodies (41). Homophilic antibodies with specificity for phosphorylcholine (PC) are superior in protecting againstStreptococcus pneumoniaeinfection (42). Homophilic anti-PC antibodies are also highly effective.