Proposed model of human B-cell development. We propose that B cells emigrating from the BM to the periphery are CD21^lo transitional/T1 B cells, which subsequently differentiate into CD21^hi transitional/T2 B cells. This maturation step requires Btk, indicating a role for BCR engagement, and is accompanied with improved survival and the potential to proliferate and differentiate into Ig-secreting cells. There is also a reduction in autoreactivity, suggesting that a checkpoint for self-tolerance exists at the step between these 2 stages of transitional B-cell development. Phenotypically, the CD21^hi transitional B cells increase expression of CD21, CD23 CD44, Bcl-2, BAFF-R, and IgD. Meanwhile, expression of LEF-1, KIAA1199, Dtx-1, and AKAP12 is reduced as the cells enter the mature B-cell repertoire. CD21^hi transitional/T2 B cells then give rise to T3/prenaive CD5⁺ B cells,³⁸  which are characterized by loss of expression of CD10, high expression of CD21, but impaired extrusion of R123. The auto-reactive specificity of this population remains to be determined.