The Non-Ig Parts of the VpreB and lambda 5 Proteins of the Surrogate Light Chain Play Opposite Roles in the Surface Representation of the Precursor B Cell Receptor

The VpreB and lambda 5 proteins, together with Ig mu -H chains, form precursor BCRs (preBCRs). We established lambda 5-/-/VpreB1-/-/VpreB2-/- Abelson virus-transformed cell lines and reconstituted these cells with lambda 5 and VpreB in wild-type form or with a deleted non-Ig part. Whenever preBCRs had the non-Ig part of lambda 5 deleted, surface deposition was increased, whereas deletion of VpreB non-Ig part decreased it. The levels of phosphorylation of Syk, SLP65, or PLC- gamma 2, and of Ca2+ mobilization from intracellular stores, stimulated by mu H chain crosslinking Ab were dependent on the levels of surface-bound preBCRs. It appears that VpreB probes the fitness of newly generated VH domains of IgH chains for later pairing with IgL chains, and its non-Ig part fixes the preBCRs on the surface. By contrast, the non-Ig part of lambda 5 crosslinks preBCRs for downregulation and stimulation.