Functional effects of TBC1 domain containing kinase deletion in immortalized B cells and plasma cells

Abstract

AbstractTBC1 domain containing kinase (TBCK) is a ubiquitous protein pseudokinase highly expressed in neurons and glial cells. Mutations in TBCK disrupt nervous system function and cause a characteristic syndrome of intellectual disability and hypotonia with various other comorbidities occurring in non-nervous tissues. Previous studies have shown a vacuolation defect present in B cells from individuals with TBCK mutations, but it is unclear if this affects plasma cell differentiation or humoral immunity. Recent research has revealed that TBCK is part of the FERRY complex involved in mRNA transport and is implicated in regulating mTORC1 signaling, autophagy, and cellular processes like cell proliferation and migration. Yet, the exact role of TBCK in these processes is still not fully understood. In this study, TBCK knockout cell lines were generated to investigate its impact on B cells and plasma cells. TBCK knockout plasma cells showed reduced immunoglobulin secretion after one week in culture, suggesting a possible defect in recycling cell components or energy usage. However, more experiments are needed to confirm this observation.