Identification of a precursor to phosphatidyl choline-specific B-1 cells suggesting that B-1 cells differentiate from splenic conventional B cells invivo: Cyclosporin A blocks differentiation to B-1

The origin of B-1 cells is controversial. The initial paradigm posited that B-1 and B-2 cells derive from separate lineages. More recently it has been argued that B-1 cells derive from conventional B cells as a result of T-in dependent Ag activation, To understand B-1 cell differentiation, we have ge nerated Ig transgenic (Tg) mice using the H and L chain genes (V(H)12 and V (K)4) of anti-phosphatidyl choline (anti-PtC) B cells. In normal mice anti- PtC B cells segregate to B-1, Segregation is intact in V(H)12 (6-1) and V(H )12/V(K)4 (double) Tg mice that develop large numbers of PtC-specific B cel ls. However, if B-1 cell differentiation is blocked, anti-PtC B cells in th ese Tg mice are B-2-like in phenotype, suggesting the existence of an ag-dr iven differentiative pathway from B-2 to B-1, In this study, we show that d ouble Tg mice have a population of anti-PtC B cells that have the phenotypi c characteristics of both B-2 and B-1 cells and that have the potential to differentiate to B-1 (B-1a and B-1b). Cyclosporin A blocks this differentia tion and induces a more B-2-like phenotype in these cells. These findings i ndicate that these cells are intermediate between B-2 and B-1, further evid ence of a B-2 to B-1 differentiative pathway.