High proportion of Ig-producing cells making autoantibody in normal mice

Abstract

‘NATURAL’ serum antibodies are thought to arise as a result of stimulation by environmental antigens. Evidence suggests, however, that many such antibodies in normal healthy individuals are specific for and may be induced by a variety of self components. Many of these autoantibodies are directed against ‘buried’ or ‘enzyme-revealed’ self antigens and include those specific for mouse reproductive organs which crossreact with human group A erythrocytes¹, human and rabbit immunoglobulins treated with proteolytic enzymes^2,3, denatured DNA⁴, enzyme-treated human lymphocytes and erythrocytes^5–8, and mouse erythrocytes treated with the proteolytic enzyme bromelain⁹. This widespread occurrence of autoantibodies could suggest that the normal immune system is preoccupied in reacting against self antigens. One way of measuring the extent of this reactivity is to compare the number of B cells making a given autoantibody(s) with the total number of B cells producing immunoglobulin (Ig) irrespective of specificity. We have previously shown that normal conventional and germ-free mice possess in their spleens considerable numbers of PFC against bromelain-treated isologous mouse erythrocytes (BrM), an ‘internal’ antigen of mouse erythrocytes^9,10. We have measured the proportion of Ig-secreting cells in the lymphoid organs of normal CBA/H mice forming PFC against BrM and found that in some (but not all) major lymphoid organs between 1% and >50% of the existing or potential Ig-secreting cells are specific for BrM.