4 The sinusoids themselves represent a niche supportive of B-cell survival and immature B cells load inside sinusoids before leaving for the periphery. 1, 3 Recently, it has been demonstrated that reduced responsiveness of immature and transitional B cells to CXCL12, mediated by downregulation of the receptor CXC chemokine receptor 4 (CXCR4), attracts them to bone marrow sinusoids and eventually into circulation. 1, 2 Another group of stromal cells produces CXC chemokine ligand 12 (CXCL12), a chemokine regulating early pre-pro-B-cell generation as well as the movement and homing of all B-cell progenitors within the bone marrow. For example, parenchymal stromal cells have been shown to secrete IL-7, which is critical for the differentiation and proliferation of pre-B cells. It is well recognized that a variety of cellular and secreted factors within this organ collaborate to provide niches important in maintaining normal B-cell development. Furthermore, our study indicates that conversion to a state of emergency granulopoiesis is temporally delayed, allowing B cells opportunity to respond to antigen.įor the majority of adult mouse and human B cells, development occurs in the bone marrow before final splenic maturation. These data highlight the rapidity with which peripheral inflammation modifies the marrow compartment, and demonstrate that such modifications regulate acute IgM production within this organ. Disrupting homing dynamics with a CXC chemokine receptor 4 inhibitor reduced the formation of IgM-secreting cells. Concurrently, a number of B-cell survival and differentiation factors are elevated to produce a transiently supportive milieu. This response correlates with enhanced sensitivity to CXC chemokine ligand 12 (CXCL12) but not CXCL13 or CC chemokine ligand 21. Here, we show that within a few hours of challenging mice with adjuvant or cecal puncture, B cells accumulate in the bone marrow redistributed away from sinusoid vessels. This discrepancy is currently unresolved and a complete characterization of early perturbations in the B-cell niche has not been undertaken. Despite these conditions, a subset of marrow B cell remains to become activated and produce potent acute immunoglobulin M (IgM) responses. Systemic inflammation perturbs the bone marrow environment by evicting resident B cells and favoring granulopoiesis over lymphopoiesis.
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