Loss of Rab8a in B cells leads to increased antibody responses and class-switch recombination

Abstract

Rab8a is a small GTPase with a wide range of reported functions in different cell types, including vesicle recycling, vesicle traffic to cilia, cell ruffling, migration, neurite outgrowth, Toll-like receptor signalling and T cell receptor docking at the immune synapse. However, the role of Rab8a in B lymphocytes has not been described to date. Here, using a conditional B cell-specific Rab8a knockout mouse model, we investigate the role of Rab8a both in vivo and in vitro. Rab8a KO mice present enhanced antibody responses to both T-dependent and T-independent immunisations. Rab8a KO cells showed normal BCR trafficking and antigen processing and presentation but however, increased class-switch recombination. While the early BCR signalling responses, such as proximal kinase activation and calcium-flux, were normal, the signalling via AKT and ERK1/2 was decreased. We propose that the lack of Rab8a alters cellular signalling leading to enhanced antibody responses and increased class-switch recombination potentially via downmodulation of the PI3K/AKT/mTOR pathway.