Mechanisms of central nervous system viral persistence: the critical role of antibody and B cells.
Contributions of humoral and cellular immunity in controlling neurotropic mouse hepatitis virus persistence within the CNS were determined in B cell-deficient J(H)D and syngeneic H-2(d) B cell+ Ab-deficient mice. Virus clearance followed similar kinetics in all mice, confirming initial control of virus replication by cellular immunity. Nevertheless, virus reemerged within the CNS of all Ab-deficient mice. In contrast to diminished T cell responses in H-2(b) B cell-deficient muMT mice, the absence of B cells or Ab in the H-2(d) mice did not compromise expansion, recruitment into the CNS, or function of virus-specific CD4+ and CD8+ T cells. The lack of B cells and lymphoid architecture thus appears to manifest itself on T cell responses in a genetically biased manner. Increasing viral load did not enhance frequencies or effector function of virus-specific T cells within the CNS, indicating down-regulation of T cell responses. Although an Ab-independent antiviral function of B cells was not evident during acute infection, the presence of B cells altered CNS cellular tropism during viral recrudescence. Reemerging virus localized almost exclusively to oligodendroglia in B cell+ Ab-deficient mice, whereas it also replicated in astrocytes in B cell-deficient mice. Altered tropism coincided with distinct regulation of CNS virus-specific CD4+ T cells. These data conclusively demonstrate that the Ab component of humoral immunity is critical in preventing virus reactivation within CNS glial cells. B cells themselves may also play a subtle role in modulating pathogenesis by influencing tropism.
Ramakrishna
Chandran
C
Department of Neurology, Keck School of Medicine, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA.
Stohlman
Stephen A
SA
Atkinson
Roscoe D
RD
Shlomchik
Mark J
MJ
Bergmann
Cornelia C
CC
D000818:Animals; D000914:Antibodies, Viral / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002465:Cell Movement / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D005260:Female; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D006517:Murine hepatitis virus / Q000254:growth & development / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology / Q000821:virology; D013118:Spinal Cord Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology; D014775:Virus Activation / Q000276:immunology; D017735:Virus Latency / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D000914:Antibodies, Viral