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 transgenic mouse model. Mice were bred on a common C57BL/6(B6) background, and expressed rearranged and hypermutated heavy and light chain transgenes encoding high-affinity receptors for the foreign antigen hen egg lysozyme (HEL). At no stage were they exposed to HEL. Variation of the Ig heavy chain construct yielded four different types of Ig transgenic mice in which developing B lineage cells either expressed mu(m) and delta(m) in the normal physiological sequence (mu(m) then mu(m) + delta(m)), or produced mu(m) alone, delta(m) alone or mu(m) + delta(m) from the onset of heavy chain expression in the bone marrow, Immature B220(low),HSA(high) and mature B220(high), HSA(low) B cells were produced 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 cell 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 reduction 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 marrow respectively. By contrast, normal maturationally regulated expression of delta(m) led to the presence of increased numbers of mature B cells in the spleen and lengthened the average lifespan of these cells as determined by in vivo incorporation of 5-bromo-2'-deoxyuridine. These results pointed to selective effects of mu(m) and delta(m) heavy chains on regulation of the early and late stages of B cell development respectively, and provided a rational basis for co-expression of mu(m) and delta(m) as well as the delayed expression of delta(m) during normal B cell development.