![]() ![]() In addition to presenting the content of disparate publications, efforts will be made to highlight open questions and moot possibilities that verge on the speculative. As an understudied area at the frontier, the topic covered in the current work involves papers that potentially contradict one another, and consideration will be given to potential models that could account for the differences. This article will strive instead to provide an account of the stages on the road from naive B cells to intermediates to Ab-secreting plasma cells, adding consideration of work from the past few years in these areas and topics less covered in standard reviews to the existing foundation. Several excellent general reviews are sufficiently recent to provide overviews of metabolism in B cells and plasma cells. Nonetheless, important insights from B cell ontogeny will be omitted here, as will autoimmunity. Given the importance of these mechanisms of protection and their centrality to the efficacy of vaccines, the amount of literature on this interplay in B cells or plasma cells is remarkably small compared to the amount of literature on T cell helpers and other types of T cells. Such mechanisms act within cells at each step after emergence of the mature B lineages, leading to the survival benefits that accrue from having appropriate concentrations, locations, and specificities of antibodies. These two factors related to fitness selection are linked in part through sensing of cellular nutrients or whole-body metabolism. Salient findings of this group and others, sometimes exhibiting differences, will be summarized with regard to the journey to a distinctive metabolic program in PCs.Īlong with resistance to the effects of microbes that undermine reproductive fitness, nutrient supply is a second major limiting factor in Darwinian selection. This review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion. Nutrients in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription, translation, and metabolism. At each step, cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for nutrients. Whereas plasmablasts and plasma cells (PCs) are the primary sources of secreted Abs, the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential fates. ![]() With this backdrop, it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise, persist, and meet the challenge of secreting vast amounts of these glycoproteins. The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody (Ab) secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against infection. ![]()
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