title: An Atypical Splenic B Cell Progenitor Population Supports Antibody Production during Plasmodium Infection in Mice.
abstract: Hematopoietic stem and progenitor cells (HSPCs) function to replenish the immune cell repertoire under steady-state conditions and in response to inflammation due to infection or stress. Whereas the bone marrow serves as the primary niche for hematopoiesis, extramedullary mobilization and differentiation of HSPCs occur in the spleen during acute Plasmodium infection, a critical step in the host immune response. In this study, 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 infection with nonlethal Plasmodium yoelii 17X. Infection-derived LSK(-) cells upon transfer into naive congenic mice were found to differentiate predominantly into mature follicular B cells. However, when transferred into infection-matched hosts, infection-derived LSK(-) cells gave rise to B cells capable of entering into a germinal center reaction, and they developed into memory B cells and Ab-secreting cells that were capable of producing parasite-specific Abs. Differentiation of LSK(-) cells into B cells in vitro was enhanced in the presence of parasitized RBC lysate, suggesting that LSK(-) cells expand and differentiate in direct response to the parasite. However, the ability of LSK(-) cells to differentiate into B cells was not dependent on MyD88, as myd88(-/-) LSK(-) cell expansion and differentiation remained unaffected after Plasmodium infection. Collectively, these data identify a population of atypical lymphoid progenitors that differentiate into B lymphocytes in the spleen and are capable of contributing to the ongoing humoral immune response against Plasmodium infection.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and.
authors.forename: Debopam
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wikenheiser
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and.
authors.forename: Brian
authors.initials: B
authors.lastname: Kennedy
authors.affiliation: Division of Biomedical Sciences, University of California, Riverside, CA 92521.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: McGovern
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and.
authors.forename: Johnasha D
authors.initials: JD
authors.lastname: Stuart
authors.affiliation: Division of Biomedical Sciences, University of California, Riverside, CA 92521.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Wilson
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and jstumhofer@uams.edu.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Stumhofer
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D056724:Immunity, Humoral; D007156:Immunologic Memory; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010967:Plasmodium yoelii / Q000276:immunology / Q000502:physiology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000502:physiology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology* / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88