Final step of B-cell differentiation into plasmablasts; the right time to activate plasma cell PIM2 kinase

The differentiation of B cells into antibody-secreting plasma cells is a complex process that involves extensive changes in morphology, lifespan, and cellular metabolism to support the high rates of antibody production. During the final stage of differentiation, B cells undergo significant expansion of their endoplasmic reticulum and mitochondria, which induces cellular stress and may lead to cell death in absence of effective inhibition of the apoptotic pathway. These changes are tightly regulated at transcriptional and epigenetic levels, as well as at post-translational level, with protein modifications playing a critical role in the process of cellular modification and adaptation. Our recent research has highlighted the pivotal role of the serine/threonine kinase PIM2 in B cell differentiation, from commitment stage to plasmablast and maintenance of expression in mature plasma cells. PIM2 has been shown to promote cell cycle progression during the final stage of differentiation and to inhibit Caspase 3 activation, raising the threshold for apoptosis. In this review, we examine the key molecular mechanisms controlled by PIM2 that contribute to plasma cell development and maintenance.