Extramedullary hematopoiesis (EMH), an epiphenomenon arises during emergency situations such as infection, stress or pathological status of bone marrow to maintain homeostatic balance of hematopoiesis, induces mobilization and differentiation of hematopoietic stem and progenitor cells (HSPCs) to extramedullary niches. Although extramedullary production of myeloid and erythroid cells are very common and well-studied, instances of extramedullary lymphopoiesis are less investigated. Here, we identified an atypical HSPC population in the spleen of C57BL/6 mice, with a Lineage-Sca-1+c-kit - (LSK-) phenotype that proliferates in response to an acute infection with non-lethal Plasmodium yoelii 17X. LSK- cell expansion coincided with severe disruption of B lymphopoiesis in bone marrow, and infection-derived LSK- cells differentiated into B cells capable of entering into a germinal center reaction, and developed into memory B cells and antibody-secreting cells that were capable of producing parasite-specific antibodies. Furthermore, LSK- cells produce pro-inflammatory cytokine IL-17 to stimulate podoplanin+CD31 - fibroblast-like reticular cells (FRCs) in the spleen to produce CXCL12 and induce a microenvironment that supports its own differentiation into B cells. Splenic LSK- cell response to Plasmodium is not unique attribution to parasite infection, but LSK- cell differentiation into B cells can be triggered by lymphotrophic gammaherpesvirus MHV68. Interestingly, MHV68 shows a tropism for LSK- cells and MHV68-infected LSK - cells can serve as a conduit for long term latency maintenance of the virus. Together, the findings of this dissertation identify a novel lymphoid progenitor population in spleen of mice that can respond to the presence of the pathogen directly by differentiating into mature B cells to aide in the ongoing humoral response against the pathogen.
|Advisor:||Stumhofer, Jason S.|
|Commitee:||Cannon, Martin J., Forrest, James C., Ponnappan, Usha, Zhou, Daohong|
|School:||University of Arkansas for Medical Sciences|
|Department:||Microbiology and Immunology|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 78/11(E), Dissertation Abstracts International|
|Keywords:||Cxcl12, Extramedullary hematopoiesis, Il-17, Lsk- cells, Lymphopoiesis, Plasmodium|
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