Do Memory B Cells Form Secondary Germinal Centers? Yes and No

Abstract

Memory is the defining feature of the adaptive immune system. Humoral immune memory is largely though not exclusively generated in the germinal center (GC), which spawns long-lived plasma cells that support ongoing serum antibody titers as well as "memory B cells" (MBCs) that persist in the immune host at expanded frequencies. Upon reencounter with antigen, these MBCs are reactivated and potentially can contribute to protection by further expansion, rapid differentiation to antibody-forming cells, and/or reseeding of a new round of GCs along with somatic V region mutation and selection. Here I will discuss what controls these various potential fates of MBCs and the functional significance of different types of MBC reactivation.

Figure 1.

Comparison of the immunoglobulin (Ig) class and subset models that correlate memory B cells (MBCs) phenotype with functional potential in a secondary response. (Top) Two circles show IgM and IgG MBCs and their proposed direct correlation with germinal center (GC) and plasmablast (PB) generation, respectively. Also shown in the pie chart, although not known at the time of the original proposal (and therefore shown in faded colors), is the different composition of these two Ig classes in terms of MBCs subsets as defined by PD-L2 and CD80 expression (see text), namely, double-negative (DN) (green), single-positive (SP) (purple), and double-positive (DP) (yellow). (Bottom) Three circles show the three subsets and depict their functional potential as reported by Zuccarino-Catania et al. (2014). Conversely, their differential compositions of IgM (blue) and IgG (red) MBCs are shown in the pie chart. Because IgM MBCs are dominated by DN, they will conspicuously make GCs, whereas because IgG MBCs are dominated by DP, they will tend to make more PB responses. However, as shown at the bottom, the more precise distinctions are seen by the subset segregation, regardless of Ig isotype.