B-cell commitment, development and selection

Here we review three areas in B-cell development in the mouse, with a focus on relevance to B-1/CD5(+) B cells. Multiparameter flow cytometry has allowed the dissection of intermediate stages of developing B cells, both in fetal liver and bone marrow. In the first area, we present recent work that has delineated a fraction of pre-pro-B cells, committed to the B lineage, but lacking any immunoglobulin rearrangements. Next, the role of the pre-B-cell receptor in B-cell repertoire selection has become clear in the past few years, but we present work suggesting that thr action of this process during fetal life is different, resulting in selection of a very distinct repertoire compared with adult. Finally, we describe a new VH3609 antithymocyte Ig transgenic mouse model system that has provided the first definitive evidence for the role of self-antigen in development and maintenance of natural autoreactive B cells.