Selective maturation of VH12 B cells in the spleen enriches for anti-phosphatidyl choline B cells: evidence for receptor editing.

: PtC-specific B-1 cells originate from conventional B-2 (B-0) cells as a result of antigen activation. VH12 B cells specific for PtC are enriched at two developmental checkpoints in the bone marrow; first at the pre-BI to pre-BII transition where VH12 pre-B cells with anti-PtC VHCDR3 are enriched, and second at the pre-BII to immature B cell transition where L chain diversity is restricted. This restriction is due to the inability of most L chains to associate with VH12 H chains. We present evidence here of a third developmental checkpoint that enriches for PtC-specific B cells, at the transitional to mature B-2 (B-0) cell stage. Most VH12 transitional B cells do not differentiate to a mature B-2 cell and, of those that do, most have undergone receptor editing. The V kappa 4/5H L chain appears to be one of the few L chains that can support differentiation to the mature B-2 cell stage, providing an explanation for its dominance among VH12 B cells in the spleen. Once cells reach this stage, those that bind PtC are induced to differentiate to B-1. Thus, through selection at multiple differentiative stages and the induction of extensive secondary V kappa rearrangement and receptor editing, VH12 B cell differentiation is focused toward specificity for PtC and selection to the B-1 subset.