PMID- 21865385 OWN - NLM STAT- MEDLINE DCOM- 20111121 LR - 20220310 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 85 IP - 21 DP - 2011 Nov TI - Alphavirus-induced encephalomyelitis: antibody-secreting cells and viral clearance from the nervous system. PG - 11490-501 LID - 10.1128/JVI.05379-11 [doi] AB - Sindbis virus (SINV) infection of the central nervous system (CNS) provides a model for understanding the role of the immune response in recovery from alphavirus infection of neurons. Virus clearance occurred in three phases: clearance of infectious virus (days 3 to 7), clearance of viral RNA (days 8 to 60), and maintenance of low levels of viral RNA (>day 60). The antiviral immune response was initiated in the cervical lymph nodes with rapid extrafollicular production of plasmablasts secreting IgM, followed by germinal center production of IgG-secreting and memory B cells. The earliest inflammatory cells to enter the brain were CD8(+) T cells, followed by CD4(+) T cells and CD19(+) B cells. During the clearance of infectious virus, effector lymphocytes in the CNS were primarily CD8(+) T cells and IgM antibody-secreting cells (ASCs). During the clearance of viral RNA, there were more CD4(+) than CD8(+) T cells, and B cells included IgG and IgA ASCs. At late times after infection, ASCs in the CNS were primarily CD19(+) CD38(+) CD138(-) Blimp-1(+) plasmablasts, with few fully differentiated CD38(-) CD138(+) Blimp-1(+) plasma cells. CD19(+) CD38(+) surface Ig(+) memory B cells were also present. The level of antibody to SINV increased in the brain over time, and the proportion of SINV-specific ASCs increased from 15% of total ASCs at day 14 to 90% at 4 to 6 months, suggesting specific retention in the CNS during viral RNA persistence. B cells in the CNS continued to differentiate, as evidenced by accumulation of IgA ASCs not present in peripheral lymphoid tissue and downregulation of major histocompatibility complex (MHC) class II expression on plasmablasts. However, there was no evidence of germinal center activity or IgG avidity maturation within the CNS. FAU - Metcalf, Talibah U AU - Metcalf TU AD - Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA. FAU - Griffin, Diane E AU - Griffin DE LA - eng GR - R01 NS038932/NS/NINDS NIH HHS/United States GR - T32 AI007417/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110824 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antigens, CD) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin M) SB - IM MH - Alphavirus Infections/*immunology/*pathology/virology MH - Animals MH - Antibody-Producing Cells/*immunology MH - Antigens, CD/analysis MH - B-Lymphocytes/chemistry/immunology MH - Brain/immunology MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Encephalomyelitis/*immunology/*pathology/virology MH - Female MH - Germinal Center/immunology MH - Immunoglobulin G/immunology MH - Immunoglobulin M/immunology MH - Lymph Nodes/immunology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nervous System/immunology/pathology/virology MH - Sindbis Virus/*immunology/*pathogenicity PMC - PMC3194963 EDAT- 2011/08/26 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/05/01 CRDT- 2011/08/26 06:00 PHST- 2011/08/26 06:00 [entrez] PHST- 2011/08/26 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/05/01 00:00 [pmc-release] AID - JVI.05379-11 [pii] AID - 5379-11 [pii] AID - 10.1128/JVI.05379-11 [doi] PST - ppublish SO - J Virol. 2011 Nov;85(21):11490-501. doi: 10.1128/JVI.05379-11. Epub 2011 Aug 24.