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

Abstract

BCL1, a spontaneous surface IgM (mu lambda)-positive (sIgM+) B cell leukemia of BALB/c (Igha) origin rarely grows in the Ig heavy chain (Igh) congenic mouse C.B-20 (Ighb) 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 (Igha/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 BCL1 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 lambda or kappa 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 mu-chain appeared to make the major contribution to the idiotypic determinant because a hybridoma product composed of BCL1 mu-chains and BALB/c kappa-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.

• Authors: R P Ciavarra, E S Vitetta, J Forman
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 137 Issue 4 Pg. 1371-5 (Aug 15 1986) ISSN: 0022-1767 [Print] United States
• PMID: 2426362 (Publication Type: Journal Article)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Neoplasm
• Epitopes
• Immunoglobulin Heavy Chains
• Immunoglobulin Idiotypes
• Immunoglobulin M
• Immunoglobulin Variable Region
• anti-IgM

Topics

• Animals
• Antibodies, Anti-Idiotypic (biosynthesis)
• Antibodies, Neoplasm (biosynthesis)
• B-Lymphocytes (immunology, pathology)
• Cell Division
• Epitopes (genetics)
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Idiotypes (immunology)
• Immunoglobulin M (biosynthesis)
• Immunoglobulin Variable Region (genetics)
• Leukemia, Experimental (genetics, immunology, therapy)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C