Perspective
Effects of Acute and Chronic Inflammation on B-Cell Development and Differentiation

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Recently, our understanding of hematopoiesis and the development of the immune system has fundamentally changed, leading to significant discoveries with important clinical relevance. Hematopoiesis, once described in terms of irreversible and discrete developmental branch points, is now understood to exist as a collection of alternative developmental pathways capable of generating functionally identical progeny. Developmental commitment to a particular blood-cell lineage is gradually acquired and reflects both cell intrinsic and extrinsic signals. Chief among the extrinsic factors are the environmental cues of hematopoietic microenvironments that comprise specific “developmental niches” that support hematopoietic stem and progenitor cells. Most of this new understanding comes from the study of normal, steady-state hematopoiesis, but there is ample reason to expect that special developmental and/or differentiative mechanisms operate in response to inflammation. For example, both stem and progenitor cells are now known to express Toll-like receptors that can influence hematopoietic cell fates in response to microbial products. Likewise, proinflammatory cytokines mobilize hematopoietic stem cells to peripheral tissues. In this Perspective, we review inflammation's effects on central and extramedullary B lymphopoiesis and discuss the potential consequences of peripheral B-cell development in the context of systemic autoimmune diseases.

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Editor's Note

In 1621 Fabricius ab Aquapendente described a sac-like structure over the terminal gut in birds, known ever since as the bursa of Fabricius (Ribatti et al., 2006). In 1954 Glick and Chang found that immunized chickens in which the bursa of Fabricius was removed early in development did not develop antibodies, establishing this structure as critical to antibody development (Ribatti et al., 2006). These observations were followed by the work of Cooper and Good, who suggested a functional division of immune cells, with bursal (B) cells responsible for antibody production and thymus (T) cells responsible for delayed-type hypersensitivity (Cooper et al., 1965). Over the ensuing decades B cells have been found to play a critical role in antibody formation, T cell function and immune regulation (LeBien and Tedder, 2008). Recent development of the monoclonal antibody rituximab, which is directed against a subset of B cells, has resulted in a heightened interest in B cells as a target for the treatment of autoimmune disease. In this issue Cain and colleagues report on the role of acute and chronic inflammation in B cell development, Manjarrez-Orduño et al focus on the role of B cells in the development of immunological tolerance, and Nagel et al provide insight into the potential for B-cell directed therapy of inflammatory mediated skin diseases. In one of the first reviews of the roles of T and B lymphocytes, Martin Raff wrote that “…insight into the functioning of the immune system… has paved the way for rational attempts to manipulate selectively the different cell typesyfor the benefit of patientsy” (1973). These Perspectives outline advances towards the fulfillment of Raff's prediction. Russell P. Hall, III, Deputy Editor