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In this talk I will summarise our recent work mapping the activated B cell protein landscape. Using high resolution quantitative mass spectrometry we have explored how immune activation and the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) regulate the proteome of B lymphocytes to control B cell differentiation. Triggering the B cell receptor in combination with co-stimulatory signals and cytokines induces considerable proteome re-modelling and our data reveals the metabolic and protein synthesis machinery and environmental sensors that shape B cell fate. We show that mTORC1 activity is critical for the expression of transcription factors that regulate B cell differentiation and metabolism, including aryl hydrocarbon receptor (AHR) and MYC. Inhibiting mTORC1 activity also impairs the expression of nutrient and amino acid transporters. This work provides a detailed map of naïve and immune activated B cell proteomes, and a resource for exploring and understanding the cellular machinery that direct B cell phenotypes.
