![]() ![]() In contrast, B lymphocyte-derived IL-35 was detrimental in the context of Salmonella infection as its deletion led to enhanced monocyte and T lymphocyte responses upon infection ( 21). cruzi infection and dampening of infection-associated inflammation following pathogen clearance ( 20). In this regard, B lymphocyte derived IL-17 was absolutely required for efficient control of T. Similarly, recent studies in mice examining responses to infectious agents such as Trypanosoma cruzi and Salmonella enterica have demonstrated the propensity of PCs to express cytokines such as interleukin (IL)-17 ( 20) as well as IL-35 and IL-10 ( 21), respectively. Transcriptional analysis of these cells further supported the idea that IRA B cells may be a bona fide subset of PCs as their gene signature clustered closest to PCs compared to other B cell subsets. Phenotyping of IRA B cells demonstrated the expression of the PC marker, CD138. In a landmark study, it was shown that stimulation of mice with lipopolysaccharide (LPS) led to the generation of a population of granulocyte-macrophage colony-stimulating factor (GM-CSF) producing cells referred to as innate response activator (IRA) B cells ( 19). However, this viewpoint has now been challenged ( Figure 1). More than Just Antibody Factories Regulation of Infectious and Autoimmune Immune Responsesįor decades, it has been presumed that upon maturation, PCs migrate to the bone marrow (BM) where they remain quiescent and ONLY secrete copious amounts of Abs. Furthermore, we consider the long-term effects of these cells on various biological processes including aging and introduce strategies that may become key means of modulating PC functionality for a beneficial outcome. This Perspective highlights the evolving functions of PCs and discusses the potential for environmental interactions to program these diverse regulatory behaviors. ![]() However, the field has recently begun to appreciate the multitude of functions that PCs possess aside from Ab secretion ( 15– 18). Not surprisingly, numerous studies have focused on the induction of PCs differentiation from the perspective of generating antigen-specific Ab responses ( 14). As such, the accumulation of these cells over a lifetime potentially represents a historical record of humoral immune responses. This latter phenotype being thanks in part to an expanded Golgi-network that provides PCs with their signature peri-nuclear halo when viewed under a microscope ( 13). Given this, it can be rationally perceived that PCs sit at the apex of adaptive immunity in the sense that these cells have the potential to survive indefinitely in both mice ( 6– 9) and humans ( 10– 12) while also continuously secreting Abs ( 9). In contrast, the durability of an immune response results from the formation of long-term immunological “memory” which includes cell types such as memory B and T lymphocytes ( 4) as well as plasma cells (PCs) ( 5).Ī significant goal upon vaccination or infection is the production of protective Abs for a sustained period of time. In the case of B lymphocytes, this antigenic diversity can be further modified via somatic hypermutation (SHM) ( 2) and class switching ( 3) during a subsequent immune response. The former is initiated early in B and T lymphocyte development and is driven by V(D)J recombination of antigenic gene loci ( 1). Trademarks of the adaptive immune system include the ability to respond to diverse sets of antigenic stimuli and the long-term durability of this response. Furthermore, we discuss potential applications of PC immunotherapy and its implementation for translational benefit. Here we summarize the current understanding of PC biology focusing on their ever-growing functional repertoire independent of Ab production. In part, PCs accomplish this by integrating extrinsic signals from their environment which dictate their downstream functionality. This is highlighted by recent studies showing that PCs function as key regulators of processes such as hematopoiesis as well as neuro-inflammation. However, it is now appreciated that PCs can have far reaching effects on pathologic as well as non-pathologic processes independent of Ab secretion. These cells are most recognizable for their extended lifespan as well as their ability to secrete large amounts of antibodies (Abs) thus positioning this cell type as a key component of humoral immunity. Plasma cells (PCs) represent the terminal differentiation step of mature B lymphocytes. School of Medicine, Kalamazoo, MI, United States Department of Biomedical Sciences, Center for Immunobiology, Western Michigan University Homer Stryker M.D. ![]()
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