VIRUS SPECIFICITY AND ISOTYPE EXPRESSION OF INTRAPARENCHYMAL ANTIBODY-SECRETING CELLS DURING SINDBIS VIRUS ENCEPHALITIS IN MICE

To study the generation of specific antibody responses within the cent ral nervous system (CNS), we have utilized a murine model of acute vir al encephalitis. When Sindbis virus (SV) is injected intracerebrally i nto weanling mice it causes an acute non-fatal encephalitis and recove ry 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 e ncephalitis. The numbers of SV-specific ASC peak early in spleen and l ymph nodes and then begin to increase in brain, suggesting that initia l stimulation of B cells occurs primarily in peripheral lymphoid tissu e followed by B cell entry into the circulation and appearance in the brain. The pattern for each individual isotype was similar with peak n umbers of SV-specific cells present in the spleen 5-7 days after infec tion, while numbers in the brain continue to rise through day 20 when most ASC were secreting IgG2a or IgA SV-specific antibody. The data su ggest therefore that most isotype switching from IgM to IgG and IgA oc curs in peripheral lymphoid tissue. An exception to this pattern is Ig G1, where numbers of ASC producing IgG1 do not show a peak in spleen a nd 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 recruitm ent of ASC into the CNS is non-specific. However, the percentage of AS C that are specific for SV structural proteins rises steadily througho ut the course of encephalitis suggesting that retention of ASC in the CNS is specific or that some portion of the SV-specific antibody respo nse is generated within the CNS.