Fas Is Required for Clonal Selection in Germinal Centers and the Subsequent Establishment of the Memory B Cell Repertoire

In T cell–dependent immune responses, high-affinity B cells are selected and differentiate into memory cells; however, the mechanism behind this process remains largely unknown. Here, we report that the selection of high-affinity B cells within germinal centers (GCs) is impaired in Fas-deficient lpr mice in the primary response, probably owing to inefficient negative selection. The memory compartment in control mice is mostly established by precursors generated from the early GCs, whereas the lpr defect expands the memory compartment by the increased recruitment of newly generated precursors from the late GCs, resulting in the accumulation of heavily mutated memory B cells at high frequency. These results suggest that Fas is required for clonal selection within GCs and the establishment of the memory B cell repertoire.