Monoclonal Antibodies

Abstract

The vast majority of antigens, when injected into an immunocompetent organism, induce a large number of distinct B-cell clonotypes (each committed to the production of a unique type of immunoglobulin) to divide and differentiate into antibody-secreting B-cell clones. Consequently, the antiserum will be composed of many distinct antibody populations which, depending on their relative concentrations, will determine the effector functions and overall antigenic specificity exhibited by the given antiserum. This polyclonality of antisera has been a major problem in viral immunology. It has been notoriously difficult and often impossible to generate antisera specific for individual viral proteins because the latter required purification procedures that, firstly, had to be stringent enough to produce a preparation of highest purity of a given viral protein and, secondly, did not result in the alteration of immunogenic and antigenic properties associated with the native structure of the given viral protein. More importantly, the polyclonality of antisera precluded, with rare exceptions, characterization of distinct antigenic regions on an individual viral protein and examination of the antiviral functions mediated by antibodies binding to these regions. Initial attempts to bypass the problems associated with polyclonal antisera by isolation, in tissue culture, of normal B-cell clones secreting antibodies of desired specificity were hampered by the fact that isolated precursor B cells gave rise to relatively small numbers of antibody secreting progeny cells.