The B cell antigen receptor (BCR) is a multi-protein complex on the surface of B cells that consists of a membrane bound immunoglobulin (mlg) and a non-covalently associated heterodimer, Ig-alpha/Ig-beta. Each mature B cell expresses multiple copies of a BCR specific for a unique antigen. Crosslinking of the BCR by multivalent antigens initiates a signaling cascade that leads ultimately to cellular proliferation and differentiation into antibody-secreting plasma cells and memory B cells. The B cell coreceptor complex of CD19 and CD21 functions synergistically with the BCR to reduce the threshold for B cell activation. This proposal outlines a strategy for the design and synthesis of multivalent scaffolds that display multiple antigenic epitopes for the BCR and C3d peptide mimetics that bind to CD21. These ligands will allow us to begin to elucidate the structural requirements for CD19/CD21 signal amplification. ? ?
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Puffer, Erik B; Pontrello, Jason K; Hollenbeck, Jessica J et al. (2007) Activating B cell signaling with defined multivalent ligands. ACS Chem Biol 2:252-62 |