The M603 idiotype is lost in the response to phosphocholine in terminal deoxynucleotidyl transferase-deficient mice.
The majority of anti-phosphocholine (PC) antibodies induced by the PC epitope in Proteus morganii (PM) express the M603 idiotype (id), which is characterized by an invariant Asp to Asn substitution at the V(H):D(H) junction. To elucidate the molecular basis by which M603-like B cells acquire the mutations resulting in this invariant substitution, we analyzed the immune response to PC-PM in terminal deoxynucleotidyl transferase (TdT) gene knockout (KO) mice. In the absence of TdT, T15-id antibodies comprised 80-100% of the primary response to PC-PM. Less than 10% of the response in wild-type mice is T15-id(+). In TdT KO mice, the secondary response to PC-KLH was higher than in wild-type mice and was dominated by the germ-line T15-id. About 10% of this response, in both TdT KO and wild-type mice, comprised M167-id(+) antibodies. Additionally, none of the functionally rearranged V1/DFL16.1/J(H)1 cDNA isolated from PC-PM-immunized TdT KO mice showed the Asp/Asn substitution characteristic of PC-binding, PC-PM-induced M603-like antibodies. These data indicate that production of M603-id antibody is TdT dependent, while generation of M167-id antibody is TdT independent, and that in the absence of competition from M603-like B cells, T15-id B cells can respond to PC-PM.
Mi
Qing-Sheng
QS
Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore 21224, USA.
Rezanka
Louis J
LJ
Lustig
Ana
A
Zhou
Li
L
Longo
Dan L
DL
Kenny
James J
JJ
D019943:Amino Acid Substitution; D000818:Animals; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D004253:DNA Nucleotidylexotransferase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000939:Epitopes / Q000276:immunology; D015723:Gene Library; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010767:Phosphorylcholine / Q000276:immunology*; D011511:Proteus / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D010767:Phosphorylcholine; D006433:Hemocyanins; D004253:DNA Nucleotidylexotransferase; C032808:keyhole-limpet hemocyanin