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 recycling, vesicle traffic to cilia, cell ruffling, migration, neurite outgrowth, TLR signalling and TCR 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 increased marginal zone B cells in the spleen and 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.