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FIGURE 11-18 Somatic mutations in Ig V genes. Hybridomas were produced from spleen cells of mice immunized 7 or 14 days previously with a hapten, oxazolone, coupled to a protein and from spleen cells obtained after secondary and tertiary immunizations with the same antigen. Hybridomas producing oxazolone-specific monoclonal antibodies were isolated, and the nucleotide sequences of the V genes encoding the Ig heavy and light chains were determined. Mutations in V genes increase with time after immunization and with repeated immunizations and are clustered in the complementarity-determining regions (CDRs). The location of CDR3 in the heavy chains is approximate. The affinities of the antibodies produced also tend to increase with more mutations, as indicated by the lower dissociation constants (Kd) for hapten binding. (Modified from Berek C, and C Milstein. Mutation drift and repertoire shift in maturation of the immune response. Immunological Reviews 96:23-41, 1987, Blackwell Publishing.)

Only B cells with high-affinity antigen receptors are selected to survive

Only B cells with high-affinity antigen receptors encounter antigen on follicular dendritic cells and present antigen to Tfh cell

B cells with somatically mutated Ig V genes and Igs with varying affinities for antigen

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