MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EXPRESSION DISTINGUISHES 2 DISTINCT B-CELL DEVELOPMENTAL PATHWAYS DURING ONTOGENY

All mature B cells coexpress major histocompatibility complex (MHC) cl ass II molecules, I-A and I-E, which are restriction elements required for antigen presentation to CD4(+) T cells. However, the expression o f class II during the early stages of B cell development has been uncl ear. We demonstrate here that there is a difference in the expression of class II during murine B cell development in the fetal liver and ad ult bone marrow (BM). These differences define two distinct B cell dev elopmental pathways. The Fetal-type (FT) pathway is characterized by p re-B and immature IgM(+) B cells generated in the fetal liver which in itially lack all class II expression. In contrast, the Adult-type (AT) pathway is typified by B cells developing in the adult BM which expre ss class II molecules from the pre-B cell stage. In vitro stromal cell cultures of sorted fetal liver and adult BM pro-B cells indicated tha t the difference in I-A expression during B cell development is intrin sic to the progenitors. In addition, we show that FT B cell developmen t is not restricted to the fetal liver but occurs in the peritoneal ca vities, spleens, liver, and BM of young mice up to at least 1 mo of ag e. The AT B cell development begins to emerge after birth but is, howe ver, restricted to the BM environment. These findings indicate that th ere are two distinct B cell developmental pathways during ontogeny, ea ch of which could contribute differentially to the immune repertoire a nd thus the functions of B cell subsets and lineages.