The peripheral blood B-cell repertoire in humans and its presumptive generation. Naive B cells, the precursors of GC B cells, become activated by antigen and subsequently establish GCs. In the course of the GC reaction, class-switched and IgM-only B cells carrying antibody mutants are generated and, after selection, released into the periphery as memory B cells (upper pathway, see also text). The lower pathway represents a GC-independent generation of IgM-only cells. For the determination of mutation frequencies, sequences from previous studies16 and the present work (Table 1 and Fig 2) were considered. Indicated are also the percentages of the various subsets among PB B cells and total cell numbers in the PB of a normal adult (for calculation, see text).