Abstract
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.
MeSH Terms
Animals
Antigens
B-Lymphocytes/immunology
Binding Sites, Antibody
Cells, Cultured
Dinitrophenols
Glutamates/immunology
Immune Tolerance
Iodine Radioisotopes
Lysine/immunology
Mice
Mice, Inbred A
Peptides/immunology
Spleen
Chemicals
Antigens
Dinitrophenols
Glutamates
Iodine Radioisotopes
Peptides
Lysine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ault K A
Unanue E R
Katz D H
Benacerraf B
References (16)
16 references, click to expand
-
An enzymic method for the trace iodination of immunoglobulins and other proteins.
Biochem J. 1969 Jun;113(2):299-305
PMID: 4185494
-
The effect of the carrier protein on the immune response and on the induction of tolerance in mice to the 2,4-dinitrophenyl determinant.
Immunology. 1969 Dec;17(6):819-29
PMID: 4195526
-
Induction of immunological tolerance by a hapten (DNP) bound to a non-immunogenic protein carrier.
Nat New Biol. 1971 Apr 7;230(14):180-2
PMID: 4928923
-
Carrier function in anti-hapten antibody responses. IV. Experimental conditions for the induction of hapten-specific tolerance or for the stimulation of anti-hapten anamnestic responses by "nonimmunogenic" hapten-polypeptide conjugates.
J Exp Med. 1971 Jul 1;134(1):201-23
PMID: 4397662
-
Nonantigenicity and immunologic tolerance: the role of the carrier in the induction of tolerance to the hapten.
J Exp Med. 1971 Oct 1;134(4):1046-61
PMID: 4938448
-
Hapten-specific tolerance. Preferential depression of the high affinity antibody response.
J Exp Med. 1972 Sep 1;136(3):426-38
PMID: 5065752
-
Ligand-induced movement of lymphocyte membrane macromolecules. I. Analysis by immunofluorescence and ultrastructural radioautography.
J Exp Med. 1972 Oct 1;136(4):885-906
PMID: 4626851
-
Inhibition of secondary anti-hapten responses with the hapten conjugated to type 3 pneumococcal polysaccharide.
Eur J Immunol. 1972 Oct;2(5):460-7
PMID: 4117341
-
Immunological tolerance in bone marrow-derived lymphocytes. I. Evidence for an intracellular mechanism of inactivation of hapten-specific precursors of antibody-forming cells.
J Exp Med. 1972 Dec 1;136(6):1404-29
PMID: 4539311
-
Immunological tolerance to a hapten. I. Induction and maintenance of tolerance to trinitrophenyl with trinitrobenzene sulfonic acid.
J Exp Med. 1973 Jan 1;137(1):42-54
PMID: 4120095
-
The allogeneic effect in inbred mice. 3. Unique antigenic structural requirements in the expression of the phenomenon on unprimed cell populations in vivo.
J Exp Med. 1973 Apr 1;137(4):991-1008
PMID: 4571330
-
Induction of B cell tolerance in vitro to 2,4-dinitrophenyl coupled to a copolymer of D-glutamic acid and D-lysine (DNP-D-GL).
J Exp Med. 1973 Jul 1;138(1):312-7
PMID: 4577621
-
Redistribution and fate of Ig complexes on surface of B lymphocytes: functional implications and mechanisms.
Transplant Rev. 1973;14:184-210
PMID: 4580724
-
Hapten-specific tolerance: unresponsiveness in the T cell-depleted population.
Eur J Immunol. 1973 Jul;3(7):457-60
PMID: 4586172
-
Events after the binding of antigen to lymphocytes: removal and regeneration of the antigen receptor.
J Exp Med. 1974 May 1;139(5):1110-24
PMID: 4596511
-
Immunological tolerance in bone marrow-derived lymphocytes. II. Effects of allogeneic cell interactions and enzymatic digestion with trypsin or inactivated hapten-specific precursors of antibody-forming cells.
J Exp Med. 1974 Jun 1;139(6):1446-63
PMID: 4133614