Overcoming the dichotomy of quantity and quality in antibody responses

Germinal centers (GCs) are specialized environments in which B cells mutate their BCR to identify new Abs with high affinity to a challenging Ag. B cells are selected in an evolutionary process of multiple rounds of mutation and selection. In the past decade, mechanisms of B cell migration, division, mutation, selection, and final differentiation have been extensively studied. Thereby, modulations of these mechanisms either optimize the quality, in terms of affinity, or the quantity of generated Abs, but never both, leading to an unclear effect on the overall efficiency of the Ab response. In this article, we predict with mathematical models that an affinity-dependent number of GC B cell divisions overcomes the dichotomy of quality and quantity, and has to be considered as a good target for immune interventions, in particular, in the elderly population with poor GC responses.