High-affinity BCR facilitates extrafollicular plasma cell generation (short- and long-lived plasma cells, i.e., SLPCs and LLPCs), with AMPK then restraining rates of protein synthesis (upper left), but memory B cells (MBCs) can also arise. mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion. 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. Keywords: B lymphocyte, Plasma cell, Intermediary metabolism, Glucose, Glutamine, Fatty acid, Signal transduction Subject terms: Germinal centres, Somatic hypermutation Preface Along with resistance to the effects of microbes that undermine reproductive fitness, nutrient supply is usually a second major limiting factor in Darwinian selection. These two factors related to fitness selection are linked in part through sensing of cellular nutrients or whole-body metabolism. 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. 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 usually remarkably small compared to the amount of literature on T cell helpers and other Naratriptan types of T cells. Nonetheless, important insights from B cell ontogeny will be omitted here, as will autoimmunity. Several excellent general reviews are sufficiently recent to provide overviews of metabolism in B cells [1C5] and plasma cells [6, 7]. 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. 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. In addition to presenting the content of disparate publications, efforts Naratriptan will be made to highlight open questions and moot possibilities that verge around the speculative. These will generally be marked by different conventional English tenses to distinguish generally accepted or amply replicated information (present tense), reported findings (past tense), and possibilities (a conditional voice or verb tense, without use of an active past tense). A cognitive bias in the background is the view that evolution and Darwinian fitness are likely to favor diversityeven Rabbit Polyclonal to RAB41 within one individual and certainly among immunogens and individuals. This point underscores the importance of eliminating a cultural tendency to state a body of results as being universally true despite strong evidence of variety in each class of cells and locale. Introduction and overview Pre- and postnatal ontogeny yield three classes of B cells that can progress to antibody secretionthe B1 lineage and 2 B2 lineages, follicular (FO), and marginal zone (MZ) B cells [8, 9]. However, these classes exhibit differences in their functions and molecular programs [9, Naratriptan 10]. B1 B cells, subdivided into B1a and B1b subsets, are thought to be the predominant sources of circulating immunoglobulins (Igs) termed natural antibodies, which arise without overt immune challenge [9, 11, 12]. For simplicity, this review will treat B1a and B1b cells collectively as B1 B cells despite differences between the two types. In contrast to the B2 subset, a fraction of B1 cells appears able to reprogram splicing to generate secreted natural antibodies without expression of the transcription factor Blimp1 [10]. Moreover, B1 cells are major sources of T-independent (T-I) antibodies, which rely less on conversation with or help from CD4+ T cells for secretion than other antibodies [11C14]. B1 cells are widely distributed, including in lymphoid organs, but the peritoneal cavity is usually a major site of residence [8, 15]. Peritoneal B1 cells serve in part as precursors.