DIFFERENTIAL REGULATION OF EARLY AND LATE STAGES OF B-LYMPHOCYTE DEVELOPMENT BY THE MU-MEMBRANE AND DELTA-MEMBRANE HEAVY-CHAINS OF IG

Regulation of B lymphocyte development by the mu-membrane (mu(m)) and delta-membrane (delta(m)) heavy chains of Ig was examined in an Ig tra nsgenic mouse model. Mice were bred on a common C57BL/6(B6) background , and expressed rearranged and hypermutated heavy and light chain tran sgenes encoding high-affinity receptors for the foreign antigen hen eg g lysozyme (HEL). At no stage were they exposed to HEL. Variation of t he Ig heavy chain construct yielded four different types of Ig transge nic mice in which developing B lineage cells either expressed mu(m) an d delta(m) in the normal physiological sequence (mu(m) then mu(m) + de lta(m)), or produced mu(m) alone, delta(m) alone or mu(m) + delta(m) f rom the onset of heavy chain expression in the bone marrow, Immature B 220(low),HSA(high) and mature B220(high), HSA(low) B cells were produc ed in all mice regardless of their developmental pattern of mu(m) and delta(m) expression. However, production of immature B cells was most efficient when mu(m) heavy chain was expressed alone during early B ce ll development. Thus expression of delta(m) during this period either in the presence or absence of mu(m) resulted in a 2- to 3-fold reducti on in the numbers of immature B cells in the spleen as well as altered levels of surface B220 and HSA on these cells in spleen and bone marr ow respectively. By contrast, normal maturationally regulated expressi on of delta(m) led to the presence of increased numbers of mature B ce lls in the spleen and lengthened the average lifespan of these cells a s determined by in vivo incorporation of 5-bromo-2'-deoxyuridine. Thes e results pointed to selective effects of mu(m) and delta(m) heavy cha ins on regulation of the early and late stages of B cell development r espectively, and provided a rational basis for co-expression of mu(m) and delta(m) as well as the delayed expression of delta(m) during norm al B cell development.