The Amount of BCL6 in B Cells Shortly after Antigen Engagement Determines Their Representation in Subsequent Germinal Centers

It is unknown whether the incremental increases in BCL6 amounts in antigen-activated B cells influence the unfolding differentiation before germinal center (GC) formation. By comparing shortly after immunization the distribution of conventional B cells to those enforced to express BCL6 at the upper quartile of normal and those lacking BCL6 altogether, we determined that B cell representation in the stages before the GC compartment was related to BCL6 amounts. This was not by increased proliferation or suppression of early plasmablast differentiation, but rather by preferential recruitment and progression through these early stages of B cell activation, culminating in preferential transition into GC. Once established, this bias was stable in GC over several weeks; other BCL6-regulated GC B cell behaviors were unaffected. We propose that setting BCL6 amounts very early in activated B cells will be central in determining clonal representation in the GC and thus memory populations. [Display omitted] •Low BCL6 amounts retain B cells in responses in the pregerminal center stages•Low-level BCL6 overexpression does not inhibit very early plasmablast formation•Most germinal center processes are unaffected by supranormal BCL6 amounts•B cell responses are affected by BCL6 before germinal centers form Immunization activates multiple B cell clones that then partition into different fates. Robinson et al. show that the amount of BCL6 that an individual clone expresses affects its likelihood of progressing through the early immune response stages, with BCL6 amounts determining which clones enter germinal centers to contribute to long-term immunity.