Antigen-mediated antibody interference shapes polyclonal fate

Highly mutable viruses present multiple competing antigenic targets (epitopes) with differing accessibility on the envelope protein; their geometry permits simultaneous binding of more than one antibodies. Increasing evidence suggests that seemingly passive antibodies can interfere with natural selection of B cells. But little is known about how such interference impacts polyclonal responses, especially the fate of clones that target evolutionarily conserved yet poorly accessible epitopes. We present an ecological model to account for mediated interactions between B cell lineages, which stem from physical coupling of eptiopes via an antigen molecule. We find that, under heterogeneous interference, B cells with different intrinsic fitness can coexist; antagonism among fit clones promotes expansion of unfit ones at the cost of reduced collective potency. This tradeoff, however, can be alleviated by synergy toward the unfit. This framework predicts system-level outcomes (e.g. immunodominance hierarchy) from biophysical measurements (antibody affinity and cross-interference). Our results also suggest new ways to amplify rare clones by leveraging interference structure.