Thymus-independent type 2 antigen induces a long-term IgG-related network memory.
Thymus-independent type 2 (TI-2) antigens occasionally induce long-lasting IgM memory, but do not prime for typical secondary IgG responses. However, contrary to current understanding, we detected several TI-2-induced long-term memory effects in subsequent thymus-dependent (TD) responses to the hapten 2-phenyloxazolone coupled to a protein carrier. The early primary TD response, even 3 months after TI-2 immunization, included non-mutated IgM as well as IgG antibodies exhibiting higher affinities than the Ox1 idiotype which dominates and has highest affinity in sole TD responses. The secondary exclusive IgG response 8 weeks later contained major hitherto non-observed clones. Somatic hypermutation on the normally dominant V(H)Ox1 gene was largely silenced while the associated VkappaOx1 exhibited the classical affinity-enhancing mutations, thus suggesting a separate regulation of this process for V(H) and V(L) genes. Mutations accumulated in genes which normally are rarely or non-expressed or non-mutating. First evidence is presented that receptor revision by V(H) replacement may occur during immune maturation in genetically non-engineered wildtype mice. We conclude that the TI-2 antigen-induced altered selection of TD Ag-inducible clones and its severe gene-specific influence on further somatic mutations and affinity maturation represents a network memory, which we hypothesize to be mediated by anti-idiotypic regulatory T cells.
Lange
Hans
H
Biochemical Institute of the Medical Faculty, Christian-Albrechts-Universität Kiel, Otto Meyerhof-Haus, Rudolf Höberstrasse 1, Kiel, Germany.
Zemlin
Michael
M
Tanasa
Radu Iulian
RI
Trad
Ahmad
A
Weiss
Thomas
T
Menning
Hauke
H
Lemke
Hilmar
H
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D000955:Antigens, T-Independent / Q000276:immunology*; D002999:Clone Cells; D045142:Cross-Priming / Q000276:immunology; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010081:Oxazolone / Q000031:analogs & derivatives / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D013950:Thymus Gland / Q000276:immunology; D013997:Time Factors
D000906:Antibodies; D000955:Antigens, T-Independent; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; C018361:2-phenyloxazolone; D010081:Oxazolone