  The affinity of antibodies (Abs) produced in vivo for their target antigens
(Ags) is typically well below the maximum affinity possible. Nearly 25 years
ago, Foote and Eisen explained how an 'affinity ceiling' could arise from
constraints associated with the acquisition of soluble antigen by B cells.
However, recent studies have shown that B cells in germinal centers (where Ab
affinity maturation occurs) acquire Ag not in soluble form but presented as
receptor-bound immune complexes on follicular dendritic cells (FDCs). How the
affinity ceiling arises in such a scenario is unclear. Here, we argue that the
ceiling arises from the weakest link of the chain of protein complexes that
bridges B cells and FDCs and is broken during Ag acquisition. This hypothesis
explains the affinity ceiling realized in vivo and suggests that strengthening
the weakest link could raise the ceiling and improve Ab responses.
