The D segment defines the T15 idiotype: the immunoresponse of A/J mice to Pneumococcus pneumoniae

Abstract

In the immune response of BALB/c mice (Igh^a) to Pneumococcus the majority of antibodies express the idiotype of the myeloma protein TEPC15 (T15). In contrast mice of the A/J strain (Igh^e) do not express this idiotype. Using (BALB/c × A/J)F₁, F₂ or backcross mice it could be shown that in allotype heterozygous animals (Igh^a/e) Pneumococcus pneumoniae preferentially stimulates B cells expressing a heavy chain (H) encoded by genes in the BALB/c H chain gene complex. Phosphorylcholine (PC)‐specific hybridoma lines were established from BALB/c and A/J spleen cells and idiotypically analyzed using monoclonal antibodies (mAb) specific for the T15 idiotopes 32/65, 10/13, 16/13 or 21A5. Whereas the majority of the BALB/c PC‐binding mAb express these idiotopes, only some of the A/J mAb are positive for one or the other of the idiotopes formed by the variable (V) regions of the H and the light chain of the myeloma protein T15. However, 80% of the A/J PC‐binding hybridoma proteins were bound by the anti‐idiotopic mAb 21A5. This mAb is specific for a determinant partially formed by the C_α and partially by the V regions of the myeloma protein T15. The mRNA of one of these T15⁻ A/J PC‐binding hybridoma lines was sequenced. V_H and V_x were identical with sequences found for BALB/c T15‐like antibodies. The sequence of the D segment was structurally very different. The importance of the D segment in the dominant expression of the T15 idiotype is discussed.