Differential regulation of early and late stages of B lymphocyte development by the μ and δ membrane heavy chains of Ig

Abstract

Regulation of B lymphocyte development by the μ-membrane (μm) and δ-membrane (δm) 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 rysozyme (HEL). At no stage were they exposed to HEL. variation of the Ig heavy chain construct yielded four different types of Ig transgenlc mice in which developing B lineage cells either expressed μm and δm in the normal physiological sequence (μm then μm+δm), or produced μm alone, μm alone or μm +δm from the onset of heavy chain expression in the bone marrow. Immature B220low, HSAhigh and mature B220high, HSAlow B cells were produced in all mice regardless of their developmental pattern of μm and δm expression. However, production of immature B cells was most efficient when μm heavy chain was expressed alone during early B cell development Thus expression of δm during this period either in the presence or absence of μm 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 δm 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'-deoxyurtdlne. These results pointed to selective effects of μm and δm heavy chains on regulation of the early and late stages of B cell development respectively, and provided a rational basis for co-expression of μm and δm as well as the delayed expression of δm during normal B cell development Show more