Growth inhibition of a B cell leukemia: Evidence implicating an anti-idiotype immune response for protective tumor immunity

BCL₁, a spontaneous surface IgM (μλ)-positive (sIgM⁺) B cell leukemia of BALB/c (Igh^a) origin rarely grows in the Ig heavy chain (Igh) congenic mouse C.B-20 (Igh^b) but is highly metastatic and lethal in the host strain of origin. Previous studies indicated that BCL₁ tumor immunity in C.B-20 mice was associated with a T cell-mediated immune response against H-40, a minor histocompatibility (H) antigen controlled by a gene linked to the Igh locus. However, we observed that BCL₁ leukemia grew progressively in BAB-14 (Igh(a/b)) mice, a strain capable of generating an anti-H-40 immune response. This suggested that anti-H-40 immunity was insufficient for protection and implied that an Igh-V (variable) region gene product was also important for GCL₁ growth inhibition. We therefore evaluated the role of two possible Igh-V region-linked gene products in BCL₁ growth inhibition; namely, an Igh-V region-linked minor H antigen or alternatively the BCL₁ IgM idiotype (Id). We could find no evidence for an Igh-V region-linked minor H antigen because immunosuppressed (500 R) CB-20 mice reconstituted with C.B-20 anti-BAB-14 splenocytes were susceptible to BCL₁ growth, whereas recipients reconstituted with C.B-20 anti-BALB/c splenocytes were resistant to BCL₁ challenge. In contrast, C.B-20 mice immunized against purified BCL₁ IgM protein could adoptively confer BCL₁ tumor immunity. C.B-20 mice immunized against other BALB/c IgM myeloma proteins containing either λ or κ light chains failed to protect C.B.-20 mice suggesting that recognition of a unique determinant (Id) and not an allotype was crucial for tumor immunity. The BCL₁ μ-chain appeared to make the major contribution to the idiotypic determinant because a hybridoma product composed of BCL₁ μ-chains and BALB/c κ-chains still elicited BCL₁ immunity. Adoptive transfer of C.B-20 anti-BCL₁ Id splenocytes into irradiated recipients that prevented an anti-H-40 response due to H-40 tissue expression failed to adoptively confer BCL₁ immunity. Thus, these data suggest that BCL₁ growth inhibition requires a T cell-mediated response against both H-40 and the BCL₁ Id; these responses must be elicited concurrently in the tumor-bearing host to achieve protective BCL₁ immunity.