26 Natural Activation of Autoreactive B Cells
نویسندگان
چکیده
Autoreact ive, immunocompe ten t B lymphocytes in peripheral lymphoid organs have long been considered "abnormal," as it was believed that such "forbidden clones" were normally deleted or inactivated in mature reper toi res (1-3). In fact, for the last 10 years autoreact ive B cells were shown to exist in available reper toi res by the appearance o f autoantibodies in graft vs. host disease and upon systemic injection of B cell mitogens (4-8). It was believed, however, that such autoreact ive B cells were resting lymphocytes in physiological conditions. More recently, the repeated finding o f auto-antibodies in the sera o f normal individuals led to the suggestion that some autoreact ive B cells could be activated in the internal env i ronment (9-1 1). Independen t approaches have provided considerable evidence for au tonomous activities in the immune system. Even in germ-free mice maintained with low molecular weight, chemically def ined diets, there is a considerable level o f internal activation within the various lymphocyte compar tments (12-14). In what concerns B lymphocytes, these mice show normal frequencies o f activated blasts and of ef fec tor high-rate Ig-secreting cells. As the activation o f immunocompetent lymphocytes is dependen t upon stimulations and interactions with their immediate envi ronment , which are driven by clonally distr ibuted surface receptors, we could expect that the reper to i re of these internally activated B cells would not be a r andom sample o f the available ant ibody reper toi re , but ra ther would be biased to components of the organism. Here we investigate the reper to i re of naturally activated B cells, as compared with that of small resting B lymphocytes, in the same individuals. Taking as criteria for activation the size o f cells ("large cells"), their effector function (i.e., their ability to p roduce antibodies), and their mitotic activity in vivo, we show that most autoreact ive B cells reacting with autologous thyroglobulin and erythrocytes are activated.
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تاریخ انتشار 2003