FATE OF SURROGATE LIGHT-CHAINS IN B-LINEAGE CELLS

Biosynthesis of the immunoglobulin (Ig) receptor components and their assembly were examined in cell lines representative of early stages in human B lineage development. In pro-B cells, the nascent surrogate li ght chain proteins form a complex that transiently associates in the e ndoplasmic reticulum with a spectrum of unidentified proteins (40, 60, and 98 kD) and Bip, a heat shock protein family member. Lacking compa nion heavy chains, the surrogate light chains in pro-B cells do not as sociate with either the Ig alpha or Ig beta signal transduction units, undergo rapid degradation, and fail to reach the pro-B cell surface. In pre-B cells, by contrast, a significant portion of the surrogate li ght chain proteins associate with mu heavy chains, Ig alpha, and Ig be ta to form a stable receptor complex with a relatively long half-life. Early in this assembly process, Bip/GRP78, calnexin, GRP94, and a pro tein of similar to 17 kD differentially bind to the nascent mu heavy c hains. The 17-kD intermediate is gradually replaced by the surrogate l ight chain protein complex, and the Ig alpha and Ig beta chains bind p rogressively to the mu heavy chains during the complex and relatively inefficient process of pre-B receptor assembly. The results suggest th at, in humans, heavy chain association is essential for surrogate ligh t chain survival and transport to the cell surface as an integral rece ptor component.