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Proposed scheme of human B cell development leading to Ig gene hypermutation. Pathway I corresponds to T-dependent responses occurring in GCs. Pathway II could correspond to T-independent responses, which may include nonconventional help from natural killer or T cells. The splenic marginal zone (MZ) or equivalent sites in Peyer's patches or lymph nodes could be the site of B cell activation. Ig gene hypermutation takes place in both pathways.
