Cellular Dynamics of Memory B Cell Populations: IgM+ and IgG+ Memory B Cells Persist Indefinitely as Quiescent Cells

Despite their critical role in long-term immunity, the life span of individual memory B cells remains poorly defined. Using a tetracycline-regulated pulse-chase system, we measured population turnover rates and individual t(1/2) of pre-established Ag-induced Ig class-switched and IgM-positive memory B cells over 402 d. Our results indicate that, once established, both IgG-positive and less frequent IgM-positive memory populations are exceptionally stable, with little evidence of attrition or cellular turnover. Indeed, the vast majority of cells in both pools exhibited t1/2 that appear to exceed the life span of the mouse, contrasting dramatically with mature naive B cells. These results indicate that recall Ab responses are mediated by stable pools of extremely long-lived cells, and suggest that Ag-experienced B cells employ remarkably efficient survival mechanisms.