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. 2002 Nov 13;48(1):37–44. doi: 10.1016/0165-5728(93)90056-5

Virus specificity and isotype expression of intraparenchymal antibody-secreting cells during Sindbis virus encephalitis in mice

William R Tyor a,∗,1, Diane E Griffin a,b
PMCID: PMC7119766  PMID: 8227306

Abstract

To study the generation of specific antibody responses within the central nervous system (CNS), we have utilized a murine model of acute viral encephalitis. When Sindbis virus (SV) is injected intracerebrally into weanling mice it causes an acute non-fatal encephalitis and recovery is primarily dependent on the development of antiviral antibody. We used a modified enzyme-linked immunoassay to determine the number of antibody-secreting cells (ASC) specific for SV and their Ig isotype in brain, spleen and cervical lymph nodes over the course of the acute encephalitis. The numbers of SV-specific ASC peak early in spleen and lymph nodes and then begin to increase in brain, suggesting that initial stimulation of B cells occurs primarily in peripheral lymphoid tissue followed by B cell entry into the circulation and appearance in the brain. The pattern for each individual isotype was similar with peak numbers of SV-specific cells present in the spleen 5–7 days after infection, while numbers in the brain continue to rise through day 20 when most ASC were secreting IgG2a or IgA SV-specific antibody. The data suggest therefore that most isotype switching from IgM to IgG and IgA occurs in peripheral lymphoid tissue. An exception to this pattern is IgG1, where numbers of ASC producing IgG1 do not show a peak in spleen and continue to rise in brain through the course of acute encephalitis. The data also indicate that early in infection a large proportion of ASC in the brain are not specific for SV and demonstrate that recruitment of ASC into the CNS is non-specific. However, the percentage of ASC that are specific for SV structural proteins rises steadi throughout the course of encephalitis suggesting that retention of ASC in the CNS is specific or that some portion of the SV-specific antibody response is generated within the CNS.

Keywords: Sindbis virus, Encephalitis, Antibody-secreting cells

References

  1. Baer G.M., Gellini W.J., Fishbein D.B. Rhabdoviruses. In: Fields B.N., Knipe D.M., Channock R.M., Hirsch M.S., Melnick J.L., Monath T.P., Roizman B., editors. Virology. 2nd edn. Raven Press; New York, NY: 1990. pp. 883–930. [Google Scholar]
  2. Banfa E., Golombek S.J., Kaufman L.D., Skelly S., Weissbach H., Brot N., Elkon K.B. Association between Lupus psychosis and anti-ribosomal P protein antibodies. N. Engl. J. Med. 1987;317:265. doi: 10.1056/NEJM198707303170503. [DOI] [PubMed] [Google Scholar]
  3. Butcher E.C. Cellular and molecular mechanisms that direct leukocyte traffic. Am. J. Pathol. 1990;136:3. [PMC free article] [PubMed] [Google Scholar]
  4. Cooper M.D., Butler J.L. Primary immunodeficiency diseases. In: Paul W.E., editor. Fundamental Immunology. 2nd edn. Raven Press; New York, NY: 1989. pp. 1033–1057. [Google Scholar]
  5. Coutelier J.P., van der Logt J.T., Heessen F.W., Vink A., van Snick J. Virally induced modulation of murine IgG antibody subclauses. J. Exp. Med. 1988;168:2373. doi: 10.1084/jem.168.6.2373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cross A.H., Cannella B., Brosnan C.F., Raine C.S. Hypothesis: Antigen-specific T cells prime central nervous system endothelium for recruitment of non-specific inflammatory cells to affect autoimmune demyelination. J. Neuroimmunol. 1991;33:237. doi: 10.1016/0165-5728(91)90111-j. [DOI] [PubMed] [Google Scholar]
  7. Csser H.F., Knopf P.M. Cervical lymphatics, the blood brain barrier and the immunoreactivity of the brain: a new view. Immunol. Today. 1992;13:507. doi: 10.1016/0167-5699(92)90027-5. [DOI] [PubMed] [Google Scholar]
  8. Dalmau J., Glaus F., Rosenbaum M.K., Posner J.B. Anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuropathy. Medicine. 1992;71:59. doi: 10.1097/00005792-199203000-00001. [DOI] [PubMed] [Google Scholar]
  9. Griffin D.E., Johnson R.T. Role of the immune response in recovery from Sindbis virus encephalitis in mice. J. Immunol. 1977;118:1070–1075. [PubMed] [Google Scholar]
  10. Hirsch R.L., Griffin D.E. The pathogenesis of Sindbis virus infection in athymic nude mice. J. Immunol. 1986;123:1215. [PubMed] [Google Scholar]
  11. Jones P.D., Ada G.L. Influenza virus-specific antibody secreting cells in the murine lung during primary influenza virus infection. J. Virol. 1986;60:614. doi: 10.1128/jvi.60.2.614-619.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Levine S.R., Welch K.M.R. The spectrum of neurological diseases associated with antiphospholipid antibodies, lupus anticoagulants and anticardiolipin antibodies. Arch. Neurol. 1987;43:876. doi: 10.1001/archneur.1987.00520200078024. [DOI] [PubMed] [Google Scholar]
  13. Levine B., Hardwick J.M., Trapp B.D., Crawford T.O., Bollinger R.C., Griffin D.E. Antibody-mediated clearance of alphavirus infection from neurons. Science. 1991;254:856. doi: 10.1126/science.1658936. [DOI] [PubMed] [Google Scholar]
  14. Melnick J.L. Polioviruses, Coxsackieviruses, Echoviruses and newer Enteroviruses. In: Fields B.N., Knipe D.M., Channock R.M., Hirsch M.S., Melnick J.L., Monath T.P., Roizman B., editors. Virology. 2nd edn. Raven Press; New York, NY: 1990. pp. 549–605. [Google Scholar]
  15. Moench T.R., Griffin D.E. Immunocytochemical identification and quantitation of the mononuclear cells in the cerebrospinal fluid, meninges and brain during acute viral meningoencephalitis. J. Exp. Med. 1984;159:77. doi: 10.1084/jem.159.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Monath T.P. Flaviviruses. In: Fields B.N., Knipe D.M., Channock R.M., Hirsch M.S., Melnick J.L., Monath T.P., Roizman B., editors. Virology. 2nd edn. Raven Press; New York, NY: 1990. pp. 783–814. [Google Scholar]
  17. Moore P.M., Cupps T.R. Neurological complications of vasculitis. Ann. Neurol. 1983;14:155. doi: 10.1002/ana.410140202. [DOI] [PubMed] [Google Scholar]
  18. Moskophidis D., Lohler J., Lehmann-Grube F. Antiviral antibody-producing cells in parenchymatous organs during persistent virus infection. J. Exp. Med. 1987;165:705. doi: 10.1084/jem.165.3.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Noelle R.J., Snow E.C. Cognate interactions between helper T cells and B cells. Immunol. Today. 1990;11:361. doi: 10.1016/0167-5699(90)90142-v. [DOI] [PubMed] [Google Scholar]
  20. Oehmichen M., Gruninger H., Wietholter H., Geneie M. Lymphatic efflux of intracerebrally injected cells. Acta Neuropathol. 1979;45:61. doi: 10.1007/BF00691806. [DOI] [PubMed] [Google Scholar]
  21. Parsons L.M., Webb H.E. IgG subclass responses in brain and serum in Semliki Forest virus demyelinating encephalitis. Neuropathol. Appl. Neurobiol. 1992;18:351. doi: 10.1111/j.1365-2990.1992.tb00797.x. [DOI] [PubMed] [Google Scholar]
  22. Prineas J.W., Kwon E.E., Cho E.S. Continual breakdown and regeneration of myelin in progressive multiple sclerosis plaques. Ann N.Y. Acad. Sci. 1984;436:11. doi: 10.1111/j.1749-6632.1984.tb14773.x. [DOI] [PubMed] [Google Scholar]
  23. Schwender S., Imrich H., Dorries R. The pathogenic role of virus-specific antibody-secreting cells in the central nervous system of rats with different susceptibility to co coronavirus-induced demyelinating encephalitis. Immunology. 1991;74:533. [PMC free article] [PubMed] [Google Scholar]
  24. Sedgwick J.D., Holt P.G. A solid phase immunoenyzmatic technique for the enumeration of specific antibody-secreting cells. J. Immunol. Methods. 1983;57:301. doi: 10.1016/0022-1759(83)90091-1. [DOI] [PubMed] [Google Scholar]
  25. Sedgwick J.D., Cooke A., Dorries R., Hutchings P., Schwender S. Detection and enumeration of single antibody- or cytokine-secreting cells by the ELISA-plaque (ELISPOT) assay. In: Zola H., editor. Focus on Laboratory Methods in Immunology. CRC Press; Boca Raton, FL: 1990. p. 103. [Google Scholar]
  26. Sher A., Colley D.G. Immunoparasitology. In: Paul W.E., editor. Fundamental Immunology. 2nd edn. Raven Press; New York, NY: 1989. pp. 957–983. [Google Scholar]
  27. Smith P.K., Krohn R.I., Hermanson G.T., Mallia A.K., Gartner F.H., Provanzano M.D., Fujimoto E.K., Goeke N.M., Olson B.J., Klank D.C. Measurement of protein using Bicinchoninic acid. Anal. Biochem. 1985;150:76. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  28. Springer T.A. Adhesion receptors of the immune system. Nature. 1990;346:425. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  29. Stanley J., Cooper S.J., Griffin D.E. Monoclonal antibody cure and prophylaxis of lethal Sindbis virus encephalitis in mice. J. Virol. 1986;58:107. doi: 10.1128/jvi.58.1.107-115.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tyor W.R., Johnson R.T. Immune responses and the central nervous system. In: Specter S., Bendinelli M., Friedman H., editors. Neuropathogenic Viruses and Immunity. Plenum Press; New York, NY: 1992. pp. 15–39. [Google Scholar]
  31. Tyor W.R., Moench T.R., Griffin D.E. Characterization of the local and systemic B cell response to Sindbis virus encephalitis in normal and athymic nude mice. J. Neuroimmunol. 1989;24:207. doi: 10.1016/0165-5728(89)90118-5. [DOI] [PubMed] [Google Scholar]
  32. Tyor W.R., Stoll G., Griffin D.E. The characterization of Ia expression during Sindbis virus encephalitis in normal and athymic nude mice. J. Neuropathol. Exp. Neurol. 1990;49:21. doi: 10.1097/00005072-199001000-00003. [DOI] [PubMed] [Google Scholar]
  33. Tyor W.R., Wesselingh S., Levine B., Griffin D.E. Long-term intraparenchymal immunoglobulin secretion after acute viral encephalitis in mice. J. Immunol. 1992;149:4016–4020. [PubMed] [Google Scholar]
  34. Wekerle H., Linington C., Lassman H., Myermann R. Cellular immune reactivity within the CNS. Trends Neurosci. 1986;9:271–277. [Google Scholar]

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