Figure 2.

Enhanced elicitation of known antibodies by using primary and secondary immunogens. B cells expressing germline BCRs are activated by binding to a primary immunogen. The maturation pathway through intermediate antibody(ies) to the mature antibody is denoted by black lines. The intermediate BCR(s) cross-reacts with a secondary immunogen(s) leading to further diversification until the mature antibody is elicited. An example with eight mutations is shown where (1) denotes the space of all possible mutants for one mutation (about 200 positions × 20 residues = 4 × 10³ possible mutants); (2) (denoted by –) corresponds to x i.e., about 16 × 10⁶ etc., schematically showing the exponentially increasing number of possible mutants and complexity of possible maturation pathways.