Failure of Lymphocytes to Reexpress Antigen Receptors after Brief Interaction with a Tolerogenic D-Amino Acid Copolymer

We present data concerning a strongly tolerogenic molecule made of a copolymer of D-amino acids that is not metabolizable poly(D-glutamic acid-D-lysine). The dinitrophenyl conjugate of this molecule induces profound tolerance in dinitrophenyl-specific B lymphocytes both in vivo and in vitro. We show that dinitrophenyl-poly(D-glutamic acid-D-lysine) binds to a population of lymphocytes including those specific for dinitrophenyl, that it persists for long periods on these lymphocytes and is poorly internalized by them, and that these lymphocytes are prevented from binding other dinitrophenyl compounds. Despite prolonged culture, they do not reexpress receptors for dinitrophenyl. This behavior of dinitrophenyl-poly(D-glutamic acid-D-lysine) is contrasted to that of metabolizable antigens. This finding indicates that one mechanism of tolerance induced by nonmetabolizable antigens involves the prolonged loss of B lymphocyte receptor function.