The role of a novel VH sequence (V11) in the formation of anti-phosphocholine antibodies

Abstract

The immune response to phosphocholine (PC) in mice is highly restricted. Most anti-PC antibodies use heavy-chain variable-region (VH) sequences derived from single VH gene segment, V1. In order to investigate whether a highly homologous VH gene segment, V11, could contribute to the formation of PC-binding antibodies, we carried out chain recombination experiments with M47A, a non-PC binding myeloma protein whose H-chain is encoded by the V11 gene segment, and two PC-binding antibodies, HP101.6G6 (HP6G6) and M511. The H-chains from the non-PC-binding myeloma protein, M47A, formed a functional PC-binding site when paired with L-chains from both PC-binding antibodies. These results suggest that a second VH gene segment, V11, could theoretically be used to form PC-binding antibodies. In addition, these results provide direct evidence that a single H-chain can be used in combinatorial association with different L-chains to form antibodies of differing specificities.