The adaptor molecule SLAP and E3 ubiquitin ligase c-Cbl each regulate expression of T cell receptor (TCR)-CD3 on thymocytes. Here we provide genetic and biochemical evidence that both molecules function in the same pathway. TCR-CD3 expression was similar in the absence of SLAP and/or c-Cbl. SLAP and c-Cbl were found to interact, and their expression together downregulated CD3epsilon. This required multiple domains in SLAP and the ring finger of c-Cbl. Furthermore, expression of SLAP and c-Cbl together induced TCRzeta ubiquitination and degradation, preventing the accumulation of fully assembled recycling TCR complexes. These studies indicate that SLAP links the E3 ligase activity of c-Cbl to the TCR, allowing for stage-specific regulation of TCR expression.

The avidity of BCRs and TCRs influences signal strength during processes of lymphocyte development. Avidity is determined by both the intrinsic affinity for Ag and surface levels of the Ag receptor. The Src-like adaptor protein (SLAP) is a regulator of TCR levels on thymocytes, and its deficiency alters thymocyte development. We hypothesized that SLAP, which is expressed in B cells, also is important in regulating BCR levels, signal strength, and B cell development. To test this hypothesis, we analyzed the B cell compartment in SLAP-deficient mice. We found increased splenic B cell numbers and decreased surface IgM levels on mature, splenic B cells deficient in SLAP. Immature bone marrow and splenic B cells from BCR-transgenic, SLAP-deficient mice were found to express higher surface levels of IgM. In contrast, mature splenic B cells from BCR-transgenic mice expressed decreased levels of surface BCR associated with decreased calcium flux and activation-induced markers, compared with controls. These data suggest that SLAP regulates BCR levels and signal strength during lymphocyte development.

No abstract

No abstract

The onset of collective features is expected to occur in the high-spin structure of the light lead isotopes. We have searched for new features in lg4Pb using the '"Dy ("S, 4n) and the 15'Sm ("Ca, 4") reactions with projectiles from the Tandem accelerator at Daresbury Laboratory. The level scheme was extended to J D 34R, a much higher spin than has been observed in other investigations. The highest spin is observed in a band structure consisting of dipole transitions ending at a proposed isomeric state. We find indications of collective band structures among the high-spin states in the spin region J > 16 h. Cranked'shell model calculations were performed and the results of these are compared with shell model calculations.NUCLEAR REACTIONS 162Dy (36S, 4n), E = 155 MeV; lsoSm ('8Ca, 4"). E = 200 MeV; measured E.,, I.,, I ( c c , , ?(e), yy, y-multiplicity. lg4Pb deduced levels, decays, E,; J,r. Enriched targets, Ge, Si(Li) detectors, array of anti-Compton spectrometers, B G O ball.