A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells

Abstract

Summary There is little insight into or agreement about the signals that control differentiation of memory B cells (MBC) and long-lived plasma cells (LLPC). By performing BrdU pulse-labeling studies, we found that MBC formation preceded the formation of LLPC in an adoptive transfer immunization system, which allowed for a synchronized Ag-specific response with homogeneous Ag-receptor, yet at natural precursor frequencies. We confirmed observations in wild type (WT) mice and extended them with germinal center (GC) disruption experiments and variable region gene sequencing. We thus show that the GC response undergo a temporal switch in its output as it matures, revealing that the reaction engenders both MBC subsets with different immune effector function and, ultimately, LLPC at largely separate points in time. These data demonstrate the kinetics of the formation of the cells that provide stable humoral immunity and therefore have implications for autoimmunity, vaccine development, and for understanding long-term pathogen resistance.

Bach2 is required for B cell and T cell memory differentiation

“…The authors find that the development of memory B cells occurs 'preferentially' early during the GC response. This finding agrees with published work that tracked the responses of cells with transgenically expressed BCRs 4 and observations that the memory differentiation of B cells is relatively normal or even elevated when GC responses are abbreviated or blocked 5,6 . T he observations that the immune system can 'remember' infectious insults previously encountered and that this feature can be harnessed in the form of vaccination to protect against re-infection infection gave rise to the modern field of immunology. Long-lived effector cells, including plasma cells (the effector stage of the B cell lineage), as well as memory B cells and T cells, are critical components of immunological memory.…”

Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells

“…Within this mostly short-lived NP-specific compartment, only ~20% of cells had taken up 2NBDG (Figure 5C). At 6 weeks post-immunization, by which point most LLPCs have been formed and SLPCs diminish (Han et al, 1995; Weisel et al, 2016), the majority of NP-specific bone marrow plasma cells were 2NBDG high (Figure 5D). Given that we were unable to identify NP-specific SLPCs within the splenic 2NBDG high compartment (Figure 5C–D), it seems likely that these cells represent long-lived splenic plasma cells that have been shown to exist by others (Sze et al, 2000).…”

ZBTB32 Restricts the Duration of Memory B Cell Recall Responses

“…6A, Supplemental Fig. 4, (50)). The majority of both Zbtb32 +/+ and Zbtb32 −/− bone marrow plasma cells had incorporated BrdU at day 7, suggesting either recent proliferation or derivation from upstream proliferating precursors (Fig.…”