The extent of the repertoire of antibodies that may be potentially produced by the organism is determined by the number of VH, D H, JH, VL and JL genes that encode the variable regions of immunoglobulins and by the junctional diversity that occurs at the time of somatic rearrangement. This potential repertoire includes antibodies the antigen binding site of which may recognize external as well as autologous antigens (the later being referred to as natural antibodies), or may structurally resemble the active site of enzymes and be endowed with enzymatic activity. Under physiological conditions, B-cell clones that produce antibodies naturally endowed with catalytic activity are negatively regulated and subjected to apoptosis. Catalytic antibodies are expressed only following active immunization of the organism using haptens that are analogs of transitions states for chemical reactions, or if the physiological regulatory mechanisms that control the expression of catalytic antibody-producing B-cell clones are perturbed, e.g. in the context of pregnancy or in the course of autoimmune diseases.