308 research outputs found
Tripartite phase separation of two signal effectors with vesicles priming B cell responsiveness.
Antibody-mediated immune responses rely on antigen recognition by the B cell antigen receptor (BCR) and the proper engagement of its intracellular signal effector proteins. Src homology (SH) 2 domain-containing leukocyte protein of 65 kDa (SLP65) is the key scaffold protein mediating BCR signaling. In resting B cells, SLP65 colocalizes with Cbl-interacting protein of 85 kDa (CIN85) in cytoplasmic granules whose formation is not fully understood. Here we show that effective B cell activation requires tripartite phase separation of SLP65, CIN85, and lipid vesicles into droplets via vesicle binding of SLP65 and promiscuous interactions between nine SH3 domains of the trimeric CIN85 and the proline-rich motifs (PRMs) of SLP65. Vesicles are clustered and the dynamical structure of SLP65 persists in the droplet phase in vitro. Our results demonstrate that phase separation driven by concerted transient interactions between scaffold proteins and vesicles is a cellular mechanism to concentrate and organize signal transducers
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Doubling the PEP-II Luminosity in Simulation
Simulations show that luminosity of the PEP-II B-factory can be doubled from its present peak value of 1 x 10{sup 34}cm{sup -2}s{sup -1}. The particle simulation code BBI developed for studying beam-beam interaction was used to perform the simulations. It was first found that the parasitic collisions significantly degrade the simulated luminosity as the beam currents are increased from 3A and 1.7A to 4A and 2.2A in the low and high energy rings, respectively. The effect of changes in various accelerator parameters on luminosity was then studied in detail from a rough starting point based on analytic estimates and in the process we systematically optimized the luminosity and showed that a luminosity of over 2 x 10{sup 34}cm{sup -2}s{sup -1} is achievable within feasible limits
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Analysis of the Wakefield Effects in the PEP-II SLAC B-FACTORY
We present the history and analysis of different wake field effects throughout the operational life of the PEP-II SLAC B-factory. Although the impedance of the high and low energy rings is small, the intense high current beams generated a lot of power. The effects from these wake fields are: heating and damage of vacuum beam chamber elements like RF seals, vacuum valves , shielded bellows, BPM buttons and ceramic tiles; vacuum spikes, vacuum instabilities and high detector background; beam longitudinal and transverse instabilities. We also discuss the methods used to eliminate these effects. Results of this analysis and the PEP-II experience may be very useful in the design of new storage rings and light sources
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Changing the PEP-II Center-of-Mass Energy Down to 10 GeV and up to 11 GeV
PEP-II, the SLAC, LBNL, LLNL B-Factory was designed and optimized to run at the Upsilon 4S resonance (10.580 GeV with an 8.973 GeV e- beam and a 3.119 GeV e+ beam). The interaction region (IR) used permanent magnet dipoles to bring the beams into a head-on collision. The first focusing element for both beams was also a permanent magnet. The IR geometry, masking, beam orbits and beam pipe apertures were designed for 4S running. Even though PEP-II was optimized for the 4S, we successfully changed the center-of-mass energy (E{sub cm}) down to the Upsilon 2S resonance and completed an E{sub cm} scan from the 4S resonance up to 11.2 GeV. The luminosity throughout most of these changes remained near 1 x 10{sup 34} cm{sup -2}s{sup -1}. The E{sub cm} was changed by moving the energy of the high-energy beam (HEB). The beam energy differed by more than 20% which produced significantly different running conditions for the RF system. The energy loss per turn changed 2.5 times over this range. We describe how the beam energy was changed and discuss some of the consequences for the beam orbit in the interaction region. We also describe some of the RF issues that arose and how we solved them as the high-current HEB energy changed
Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production
Secondary antibody responses are marked by faster kinetics, improved antibody affinity and a switch from IgM to other immunoglobulin isotypes, most notably IgG, compared with primary responses. These changes protect from reinfection and represent the principle of most vaccination strategies. Yet, the molecular mechanisms that underlie B-cell memory responses are unclear. Here we show, by inactivating the immunoglobulin tail tyrosine (ITT) signalling motif of membrane-bound IgG1 in the mouse, that the ITT facilitates maintenance and reactivation of IgG-switched memory B cells in vivo. The ITT motif equips IgG-switched cells with enhanced BCR signalling capacity, which supports their competitiveness in secondary immune reactions and drives the formation of IgG-secreting plasma cells even in the absence of T-cell help. Our results demonstrate that ITT signalling promotes the vigorous production of IgG antibodies and thus provide a molecular basis for humoral immunological memory
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