γD Immunoglobulin

Abstract

In the past 15 years, much has been learned about the structure and function of different classes of antibodies from studies of monoclonal immunoglobulins formed in patients with multiple myeloma and macroglobulinemia. This is particularly true for _γD, the fourth class of human immunoglobulins. _γD was discovered as the result of the study of an unusual human myeloma protein (Rowe and Fahey, 1965a), and all subsequent investigations of _γD have depended in one or another phase on the availability of _γD myeloma proteins. Two characteristics of _γD often make it necessary to study _γD myeloma proteins rather than normal _γD. First, the concentration of _γD in the serum is very low, an average of 30 µg/ml, and, second, _γD is a labile immunoglobulin which has a great tendency to aggregate and to fragment into subunits during the isolation procedure. _γD can therefore usually not be isolated in sufficient quantities from normal blood. Probably for this reason, progress in the evaluation of the role of _γD in the immune mechanism of the body has been slow. Although the striking similarity of the structure of _γD myeloma proteins to that of the other classes of immunoglobulins has always suggested that _γD must represent a class of human antibodies, several years passed following its discovery before antibody activity in that class was reported; to date, all antibody activity has been demonstrated by indirect methods. Therefore, definite proof of antibody activity in isolated normal human _γD still remains to be shown. Since _γD does not share any of the biological activities of the other immunoglobulin classes, such as fixation of complement and induction of anaphylactic reactions in the skin, role evaluation remains difficult. It is the purpose of this chapter to review the present knowledge of human _γD immunoglobulin and to stimulate new investigations which, it is hoped, will lead to discovery of the biological role of _γD antibodies.