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Review
. 2009 Feb;129(2):266-77.
doi: 10.1038/jid.2008.286.

Effects of acute and chronic inflammation on B-cell development and differentiation

Derek Cain  1 , Motonari Kondo, Huaiyong Chen, Garnett Kelsoe
Affiliations
Review

Effects of acute and chronic inflammation on B-cell development and differentiation

Derek Cain et al. J Invest Dermatol. 2009 Feb.

Abstract

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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Figures

Figure 1
Figure 1. B cell development in bone marrow
The step-wise differentiation of hematopoietic stem cells (HSC) into immature B cells in the bone marrow is depicted. Hematopoietic lineage potential gradually decreases as HSC mature through multipotent progenitors (MPP) to common lymphoid progenitors (CLP). The differentiation potential of each progenitor type to give rise to T cells (T), B cells (B), megakaryocyte/erythroid cells (MegE), and granulocytes/macrophages (GM) is indicated. Cells that commit to the B-lineage progress through a series of additional developmental stages defined by the rearrangement of immunoglobulin genes. The stages at which the immunoglobulin heavy chain genes (IgH) and light chain genes (IgL) rearrange are shown (GL, germline configuration). For reference, Hardy’s nomenclature for murine B-cell development is shown [Ref (Hardy, 1991 #7958)].
Figure 2
Figure 2. Inflammation induces extramedullary B lymphopoiesis
A simplified schematic of hematopoiesis during normal and inflamed conditions is depicted, with B-cell development progressing from hematopoietic stem cells (HSC) through common lymphoid progenitors (CLP), pro-B cells (pro-B), pre-B cells (pre-B), immature B cells (imm B), transitional 1 B cells (T1), transitional 2 B cells (T2), and mature B cells (Mat B). From HSC, granulocyte differentiation occurs through common myeloid progenitors (CMP), myeloblasts (MB), promyelocytes (PM), and polymorphonuclear neutrophils (PMN). Toll-like receptor (TLR) signals induce HSC to develop into myeloid cells and CLP to develop into dendritic cells (DC). TNFα reduces CXCL12 and stem cell factor (SCF) expression by bone marrow stromal cells, resulting in the mobilization of developing B-lineage cells to peripheral lymphoid tissues such as the spleen, where they continue to mature.
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