IDIOPATHIC PARAPROTEINEMIA - CONSEQUENCE OF AN AGE-RELATED DEFICIENCY IN THE T-IMMUNE SYSTEM - 3-STAGE DEVELOPMENT - HYPOTHESIS

On the basis of clinical studies and recent experiments in animals, a hypothesis on the development of idiopathic paraproteinemia in three stages is presented. (i) During aging, involution of the thymus and a genetically determined selective decline in certain T-cell populations lead to an impairment of the T-cell functions. The extent and the progression of these changes may be influenced by some extrinsic factors. (ii) Consequently, cooperation with and control of B cells by the T cells becomes impaired. Restriction of heterogeneity of the immune response and excessive clonal expansions with an overshoot production of homogeneous immunoglobulins-antibodies appear as a result of this imbalance in the immune system network. (iii) The repeated mono- or oligoclonal expansions result in a higher probability for either a spontaneous or a virus-induced mutation of the regulatory genes within a given B-cell clone. In that way, a monoclonal proliferation and paraprotein production would continue, even without antigenic stimulation. This intrinsic defect in cell regulation is, however, a different one from that seen in B-cell malignancies. © 1979.