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

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, T15-id B cells can respond to PC-PM.