THE SITE AND STAGE OF ANTI-DNA B-CELL DELETION

ANTIBODIES to DNA and nucleoproteins are found in sera of individuals with systemic autoimmune disease. In the population (and in the autoim mune mouse strain MRL/lpr) there is a great variety of such antinuclea r antibodies, but individuals with systemic lupus erythematosus or sin gle MRL mice express a subset only of the antinuclear specificities fo und in the population. These observations have been interpreted to mea n that these antibodies arise by immunization(1) The oligoclonal natur e of the autoantibody response and the evidence of selection acting on somatically mutated autoantibodies favour this interpretation(2,3). S pecific activation of autoantibodies in disease implies either that au toantibodies are regulated in non-diseased individuals or that autoant igen availability is variable. The former has been demonstrated in ant i-DNA transgenic mice. In normal mice, transgene-encoded antibodies ag ainst double-stranded (ds) DNA are not expressed in serum or on B cell s(4-6). Here we describe modified anti-dsDNA transgenic mice which all ow us to study the site and developmental stage at which such B-cell r egulation occurs. This model shows that in normal mice B cells express ing anti-DNA specificity are deleted in the bone marrow at a pre-B to immature B transitional stage.