The repertoire of somatic antibody mutants accumulating in the memory compartment after primary immunization is restricted through affinity maturation and mirrors that expressed in the secondary response.
The anti-(4-hydroxy-3-nitro-phenyl)acetyl (NP) response is dominated by lambda 1 chain-bearing antibodies expressing the VH gene V186.2 in combination with the D element DFL16.1. lambda 1-positive B cells were isolated from the spleens of mice immunized with NP-chicken gamma globulin 6 wk earlier. Rearranged V186.2 genes were amplified from the genomic DNA of these cells and sequenced. In cases where the rearrangement was typical for secondary anti-NP antibodies, the VHDJH sequences were generally heavily mutated. The frequency and the nature of the nucleotide exchanges mirrored those of secondary response antibodies. V186.2 genes with other rearrangements and V186.2-related genes isolated concomitantly were essentially unmutated. These results demonstrate: (a) that somatic antibody mutants are largely restricted to a small compartment of peripheral B cells, namely, that of memory cells; (b) that the memory compartment is strongly selected for high affinity precursors and largely purged from antigen-binding loss mutants; and (c) that the repertoire of binding specificities expressed in the secondary response is established in its final form before secondary immunization.
Weiss
U
U
Institute for Genetics, University of Cologne, FRG.
Rajewsky
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006241:Haptens; D007114:Immunization; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000276:immunology*; D010648:Phenylacetates; D013154:Spleen / Q000276:immunology
D006241:Haptens; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid