Restricted Clonality and Limited Germinal Center Reentry Characterize Memory B Cell Reactivation by Boosting

Abstract

Highlights d Memory B cell reentry into germinal centers is rare under typical boost regimens d Most (>90%) B cells in secondary GCs have no prior GC experience d A clonality bottleneck restricts the diversity of recall antibody-producing cells d Most primary diversity is found in an MBC compartment not accessed by boosting

Single cell BCR and transcriptome analysis after respiratory virus infection reveals spatiotemporal dynamics of antigen-specific B cell responses

“…BLI affinity measurement showed no pattern of differential affinity between Bmem and PB. Indeed, the major determinant of affinity was the clonal family and not the cell type or number of mutations, similar to what was recently reported for Bmem recall after immunization (Mesin et al, 2020). Surprisingly, mAbs from the highly expanded clonotype 566, with more than 700 sequenced cells (>70% of all cells of M28_3) exhibited low to extremely low avidity for HA by BLI.…”

Cbls boost B cells

“…Whether pre-germinal center memory B cell differentiation is affected is not directly addressed in this study. However, antibody titers following secondary infection with intestinal parasitic helminth Heligmosomoides polygyrus bakeri are reduced, as is clearance of the worm, indicating memory B cell formation is impaired (Mesin et al, 2020). One interesting aspect of this study is that, despite high levels of Cbl and Cbl-b protein in germinal center B cells (Li et al, 2018), these ubiquitin ligases do not regulate antigen presentation in these cells.…”

The BAFFling persistence of memory B cells

“…MBCs generated during a primary immune response serve as a vital reservoir of broadly cross-reactive antibody specificities against pathogens (such as influenza) that undergo antigenic drift over time to escape recognition by preexisting LLPC-derived antibodies. MBC can mount rapid recall antibody responses, and they also have the capacity to reenter GC to undergo further affinity maturation and replenish both LLPC and MBC pools (Mesin et al, 2020;Turner et al, 2020). We now appreciate that there are multiple subpopulations of MBCs with specialized functions (see figure, panel A; Weisel and Shlomchik, 2017); in mice, PD-L2 + MBCs (some of which are also CD80 + ) harbor somatically mutated BCRs that are either class-switched or unswitched.…”

“…It is proposed that this MBC subpopulation may be important to respond to more distantly related pathogens. However, the precise circumstances under which these lower-affinity MBCs are recruited into recall responses and how they contribute to host defense remain to be fully defined (Mesin et al, 2020;Turner et al, 2020).…”