title: Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses.
abstract: 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.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada; Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Moreau
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;
authors.forename: Alexandra
authors.initials: A
authors.lastname: Berger
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;
authors.forename: Megan E
authors.initials: ME
authors.lastname: Nelles
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics and.
authors.forename: Michael
authors.initials: M
authors.lastname: Mielnik
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;
authors.forename: Caren
authors.initials: C
authors.lastname: Furlonger
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada; Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;
authors.forename: Selena Y
authors.initials: SY
authors.lastname: Cen
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; and.
authors.forename: Rickvinder
authors.initials: R
authors.lastname: Besla
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; and Peter Munk Cardiac Centre, Toronto General Research Institute, Toronto, ON, Canada.
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Robbins
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada; Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics and.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Paige
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout