title: IgM production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection.
abstract: IgM responses are well known to occur early postinfection and tend to be short-lived, which has suggested that this Ig does not significantly contribute to long-term immunity. In this study, we demonstrate that chronic infection with the intracellular bacterium Ehrlichia muris elicits a protective, long-term IgM response. Moreover, we identified a population of CD138(high)IgM(high) B cells responsible for Ag-specific IgM production in the bone marrow. The IgM-secreting cells, which exhibited characteristics of both plasmablasts and plasma cells, contributed to protection against fatal ehrlichial challenge. Mice deficient in activation-induced cytidine deaminase, which produce only IgM, were protected against fatal ehrlichial challenge infection. The IgM-secreting cells that we have identified were maintained in the bone marrow in the absence of chronic infection, as antibiotic-treated mice remained protected against challenge infection. Our studies identify a cell population that is responsible for the IgM production in the bone marrow, and they highlight a novel role for IgM in the maintenance of long-term immunity during intracellular bacterial infection.
authors.affiliation: Department of Biomedical Sciences, University at Albany, State University of New York, Albany, NY 12201, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Racine
authors.forename: Maura
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Derek D
authors.initials: DD
authors.lastname: Jones
authors.forename: Susan T
authors.initials: ST
authors.lastname: Wittmer
authors.forename: Katherine C
authors.initials: KC
authors.lastname: MacNamara
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.forename: Gary M
authors.initials: GM
authors.lastname: Winslow
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002908:Chronic Disease; D004536:Ehrlichia / Q000276:immunology; D016873:Ehrlichiosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000502:physiology; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors
chemical_list: D007075:Immunoglobulin M