The functions of the immune system are classified into the function based on cellular immune responses caused mainly by the effect of T cells and the function based on humoral immunity caused mainly by the effect of antibodies. Actually, these two functions co-operate with each other to perform immune responses. Antibodies are present as cell surface receptors on the surfaces of B cells produced in the bone marrow. It is said that the number of diverse antigens recognized by the first antibody produced in the living body reaches the order of 109 to 1011. Such antibodies (antigen receptors) recognize all antigenic determinants that may exist in environments. However, these diverse antigen receptors are generally low in their ability to bind to antigens, and in many occasions, low affinity antibodies are produced. Such antibodies can not cause sufficient immune responses.
Lymphocytes, especially B cells/immunoglobulins (antibodies) are used in various applications based on their immune responses, e.g. they are used in kits for detecting the antigens of pathogens, or as diagnostics or therapeutics. If an antibody that has high reactivity with antigen is used in such antigen-detecting drugs or various therapeutics, sensitivity to antigen will be excellent and efficacy as a therapeutic at a same dose will be great. However, no means to enhance the affinity of antibodies have been known.
When pathogens or foreign substances have entered the living body, the body recognizes them as antigens and induces highly frequent somatic mutations in the genes of the V regions of antibodies which bind directly to those antigens. Such changes require stimulation from T cells, and it is considered that stimulation is provided from activated T cells in the germinal center region. Recently, the present inventors have found a molecule designated GANP whose expression increases selectively in activated B cells of this region (WO 00/50611). This molecule directly binds to a molecule called MCM (minichromosome maintenance) having DNA helicase activity, and has RNA primase activity. Therefore, it is suggested that this molecule GANP is involved in DNA replication. However, functions of GANP in the immune system have not yet been elucidated.
USPTO Backgrounds
USPTO Backgrounds