SUBCLASS RESPONSE TO POLYSACCHARIDE ANTIGENS IN CHILDREN

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This study is designed to assess the subclass distribution and clonal diversity of antibodies to group A streptococcal carbohydrate (GAC), phosphocholine (PC) and H. influenzae type b capsular polysaccharide (PRP) in normal children, and in children with (IgG2) deficiency, asplenia, and sickle cell anemia. Studies in mice have shown that anti-polysaccharide (anti-PS) anitbodies are restricted to a particular subclass, IgG3. Normal infant mice, and a strain of immunodeficient mice, CBA/N, lack the ability to secrete antibodies of this subclass, and are susceptible to infections caused by PS encapsulated organisms. Similarly, many human anti-PS antibodies are restricted to a subclass IgG2 which is late to develop in normal children. Further, deficiencies of IgG2 have been recognized in children and adults with recurrent bacterial infections. We propose that the increased susceptibility of normal children and certain groups of patients, including those with asplenia and SS, to infections caused by PS encapsulated bacteria is due, at least in part, to IgG2 deficiency. Studies outlined in this proposal will examine the relation of IgG2 to the magnitude and clonal diversity of anti-PS antibodies in these subjects. In addition, factors responsible for increasing diversity and changes in clonal dominance observed by isolectric focusing of human anti-GAC antibodies will be analyzed. Specifically, the contributions of subclasses, light chains and idiotype expression will be examined. Finally, human hybridoma antibodies specific for GAC and PC will be produced. These will be used to study the functional capacity of various subclasses and to develop anti-idiotype reagents. The latter will serve as probes to examine the relation of particular V regions to IEF clonotype patterns, and to determine, in young children, the relation between antibody secretion and V region expression on B cell surfaces.