title: Recruitment kinetics and composition of antibody-secreting cells within the central nervous system following viral encephalomyelitis.
abstract: Infection by the neurotropic JHM strain of mouse hepatitis virus produces an acute demyelinating encephalomyelitis. While cellular immunity initially eliminates infectious virus, CNS viral persistence is predominantly controlled by humoral immunity. To better understand the distinct phases of immune control within the CNS, the kinetics of humoral immune responses were determined in infected mice. Early during clearance of the JHM strain of mouse hepatitis virus, only few virus-specific Ab-secreting cells (ASC) were detected in the periphery or CNS, although mature B cells and ASC without viral specificity were recruited into the CNS concomitant with T cells. Serum antiviral Ab and CNS virus-specific ASC became prominent only during final elimination of infectious virus. Virus-specific ASC peaked in lymphoid organs before the CNS, suggesting peripheral B cell priming and maturation. Following elimination of infectious virus, virus-specific ASC continued to increase within the CNS and then remained stable during persistence, in contrast to declining T cell numbers. These data comprise three novel findings. Rapid recruitment of B cells in the absence of specific Ab secretion supports a potential Ab-independent effector function involving lysis of virus-infected cells. Delayed recruitment relative to viral clearance and subsequent maintenance of a stable CNS ASC population demonstrate differential regulation of T and B lymphocytes within the infected CNS. This supports a critical role of humoral immunity in regulating viral CNS persistence. Lastly, altered antiviral ASC specificities following clearance of infectious virus suggest ongoing recruitment of peripheral memory cells and/or local B cell differentiation.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Shuen-Ing
authors.initials: SI
authors.lastname: Tschen
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Bergmann
authors.forename: Chandran
authors.initials: C
authors.lastname: Ramakrishna
authors.forename: Shawn
authors.initials: S
authors.lastname: Morales
authors.forename: Roscoe
authors.initials: R
authors.lastname: Atkinson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000473:pathology* / Q000821:virology; D002465:Cell Movement / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018792:Encephalitis, Viral / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000276:immunology* / Q000472:pathogenicity; D009333:Neck; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D013045:Species Specificity; D014407:Tumor Cells, Cultured
chemical_list: D000914:Antibodies, Viral