Figure 5. Bm cells as they are produced during the germinal center response (see Fig.5), will be either high affinity or low affinity B cells. High affinity B cells compete for antigen binding sites on the FDC with low affinity B cells. If a B cell cannot bind to the FDC antigen it will die a programmed cell death (apoptosis). As low affinity cells are crowded out of binding sites they become apoptotic (see arrows) and are phagocytized by the tingible body macrophages (TBM). This process is an integral part of the germinal center reaction.

(5) Germinal centers may also be produced in the late phase of the primary antibody response when antibodies to an antigen first become available (See Figs. 3 and 4). Germinal center development begins in the secondary Ab response at the time the antigen enters the body since Ab (IgG) is already available for immunecomplex formation, needed for antigen transport and Ag-trapping by FDCs.

(6) Feedback inhibition and activation. When the germinal center reaction results in the production of high levels of specific Ab, the AB feeds back to the FDC antigen and covers up the antigenic sites. At the same time the FDC dendrites form a "ball of yarn"-like structure with the immune complexes on the inside of the "ball." At that time no B cells can be activated by the FDC-Ag because the Ag is hidden. This process is feedback inhibition. After weeks, AB levels drop and to maintain equilibrium between bound and free AB, AB dissociates from the immune complexes on the FDC. The "balls" unravel and the Ag becomes exposed and a new cycle of germinal center reaction begins. This will result in bringing the AB level up and as a result immunity is maintained. This cycle may be repeated as long as there is Ag left on the FDCs. Once Ag is used up, a booster immunization may be in order.

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