Specific VDJ gene combinations contribute to the specificity of memory antibodies to the phosphorylcholine hapten.
Based on their fine specificity, two groups of antibodies against the phosphorylcholine (PC) hapten have been described. Group I antibodies react predominantly with the PC moiety of the hapten and group II are directed against the entire hapten including the azophenyl spacer to the protein carrier. We have analyzed the VH gene segment utilization of hybridomas from the memory response to PC by Southern blot analysis and nucleotide sequencing of the functional VDJ rearrangements. Three main specificities of anti-PC antibodies could be distinguished. Anti-PC hybridomas with group I fine specificity utilize the VH1-DFL 16.1-JH1 rearrangement. A major portion of group II antibodies recognized the phenyl-PC part and expressed the same VH1 gene in combination with a member of the SP2 family and JH1 or JH2. The other anti-PC antibodies either used the PJ14-DFL16-JH3 rearrangement in combination with a lambda 1 L chain or a member of the VGam3.8 VH family rearranged to the DFL16.1 and the JH3 gene segments. The PJ14 and VGam3.8 V gene expressing antibodies were directed to the phenyl group and were either not or barely inhibitable by PC chloride. Thus, specific VDJ gene combinations contribute to the fine specificity of antibodies in the memory response to the PC hapten. The use of the S107, Q52, and VGam3.8. VH gene families, together with FL16.1 or SP2 D segments and JH1, JH2, or JH3 results in different fine specificities to the PC, phenyl-PC, or the azophenyl moiety of the PC hapten. These fine specificities of the memory response use V, D, and J segments of the initial T15Id+ response in combination with gene segments usually related to phenyl specificity.
Lötscher
M
M
Swiss Institute of Allergy and Asthma Research, Davos.
Amstutz
H
H
Heusser
C H
CH
Blaser
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D015139:Blotting, Southern; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006241:Haptens; D006825:Hybridomas; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010767:Phosphorylcholine / Q000276:immunology*; D013329:Structure-Activity Relationship
D006241:Haptens; D009838:Oligodeoxyribonucleotides; D010767:Phosphorylcholine