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Systemic inflammation perturbs the bone marrow environment by evicting resident B cells and favoring granulopoiesis over lymphopoiesis. Despite these conditions, a subset of marrow B cell remains to become activated and produce potent acute immunoglobulin M (IgM) responses. This discrepancy is currently unresolved and a complete characterization of early perturbations in the B-cell niche has not been undertaken. 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 response correlates with enhanced sensitivity to CXC chemokine ligand 12 (CXCL12) but not CXCL13 or CC chemokine ligand 21. Concurrently, a number of B-cell survival and differentiation factors are elevated to produce a transiently supportive milieu. Disrupting homing dynamics with a CXC chemokine receptor 4 inhibitor reduced the formation of IgM-secreting cells. 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. Furthermore, our study indicates that conversion to a state of emergency granulopoiesis is temporally delayed, allowing B cells opportunity to respond to antigen.

Growing cancers are known to modify immune responses through suppressive mechanisms manifested within the local tumor microenvironment. Accumulating evidence indicates that secreted tumor products can also influence on distant immunological compartments, including myelopoiesis in the bone marrow. However, it is unknown if a similar effect can occur to regulate B-cell lymphopoiesis in breast cancer. Examining the MMTV-PyMT murine model of breast cancer, we show a complete block in bone marrow B-cell lymphopoiesis, which is dependent on tumor burden. We also observed an increase in the total number of splenic B cells and an elevated frequency of marginal zone B cells. By using in vitro assays of B-cell lymphopoiesis, we show that tumor-secreted molecules directly inhibit B-cell progenitor proliferation and favor maturation. These data demonstrate a profound sensitivity of B-cell lymphopoiesis to the accumulation of ectopically produced molecules during tumor growth in PyMT.