Persistence of virus-specific memory B cells in mice CNS

Abstract

IMMUNOGLOBULIN (Ig) populations detected in the cerebrospinal fluid (CSF) in chronic viral infections of the central nervous system (CNS) differ from serum Ig with regard to the relative concentration of antiviral antibodies^1–4, their light chain ratio⁵ and their heterogeneity^6,7. Such observations support the idea that antibodies are produced locally in the CNS⁸. But differences between CSF and serum Ig can also be explained in terms of the selective retention and accumulation of serum antibodies after passage across the blood–brain barrier⁹. Unequivocal proof of the local antibody production requires, however, that plasma cells, or their precursor cells, be isolated from the CNS. Intracerebral inoculation of mice with 6/94, a para-influenza type 1 virus¹⁰, induces an immunologically mediated degeneration of the white matter which is related to infiltration of the brain parenchyma by mononuclear cells^11,12. In the study reported here, cells recovered from the brains of virus-infected mice were investigated as described previously to analyse memory B cells reactive to influenza viruses^13,14. Virus-reactive memory B cells, that is immunocompetent cells able to generate, on antigenic stimulation, a clone of antiviral-antibody-producing plasma cells, were demonstrated in the brains of mice injected intracerebrally with 6/94 virus but not in the brains of mice injected intraperitoneally.