The M603 idiotype is lost in the response to phosphocholine in terminal deoxynucleotidyl transferase-deficient mice

European Journal of Immunology
Qing-Sheng MiJ J Kenny

Abstract

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, T1...Continue Reading

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Citations

Jun 11, 2011·Immunogenetics·Robert L SchelonkaHarry W Schroeder
Jun 17, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tamer I MahmoudJohn F Kearney
Dec 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tamer I Mahmoud, John F Kearney

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