Fine specificity and VJ usage of light chains in antibodies to the phosphorylcholine hapten

Abstract

In the memory response to the phosphorylcholine hapten (PC) two major groups of anti-PC antibodies with different fine specificities are elicited. Group I antibodies are mainly PC specific, whereas Group II antibodies are comprised of two specificities directed against the phenyl-PC and the phenyl moiety of the PC hapten. The VL gene usage of 17 monoclonal memory anti-PC antibodies were investigated by Southern blot analysis and nucleotide sequencing. Six out of eight Group I memory PC-specific antibodies used the same VK22-JK5 rearrangement as the major T15 primary response idiotype. One expressed a mutated JK1 and one employed another VK22 gene family member. A shift in specificity from PC (Group I) towards phenyl-PC (Group II) was accompanied with the usage of either VK1C-JK1 or VK1A-JK5 rearrangements. The phenyl-specific Group II antibodies expressed the V lambda 1-J lambda 1 L chain rearrangement in combination with VH M141 expressing H chains. In this specific segment of Group II antibodies most mutations were found. Thus four different VL genes were found to contribute to the fine specificity of memory response antibodies to the PC hapten in a clear structure-function relationship. The diversified fine specificity in the memory response derives mainly from the usage of different L chains with particular VJ rearrangements in combination with VH of the dominant initial response clonotype and is not primarily due to mutational events.