Characterization of B Cells and IA Expression in Sindbis Virus Encephalitis

Sindbis virus (SV) is an alphavirus closely related to Western equine encephalitis virus that causes an acute, nonfatal meningoencephalitis in immunologically normal and athymic mice when injected intracerebrally. The inflammatory response is characterized by subependymal and perivascular mononuclear infiltrates. These mononuclear cells include helper and suppressor T cells, B cells, and macrophages. Early in encephalitis the majority of cells are helper T cells. Initially, B cells comprise a small percentage of the total inflammatory cells, but this percentage steadily increases during the course of encephalitis. The role of T cells in recruiting B cells into the central nervous system (CNS) has not been defined. In addition, the stage of differentiation and antigen specificity of these B cells are unknown. To better characterize B cells entering the CNS and compare them with B cells in the periphery, antibodies against B cells and mouse immunoglobulin isotypes were used to immunocytochemically identify all B cells bearing these markers in the inflammatory cuffs, spleens, and peripheral blood of mice with SV encephalitis. In conjunction with our studies of B cells we examined the expression of IA antigen in the CNS of normal and athymic mice during this acute viral encephalitis. Sindbis virus encephalitis is characterized initially by B cells that express IgM or IgM/IgD (day 3 after SV inoculation). These cells for the most part are replaced later in the encephalitis (day 10-14) by B cells with IgG1, IgG2a, and IgG2b on their surfaces. This process is reflected in the spleen. Normally, B cells in the spleen express IgM and IgD, with much smaller percentages bearing the IgG and IgA isotypes. During SV encephalitis IgM-labeled B cells decrease in the spleen, and IgG2aand IgG2b-labeled B cells increase. The demonstration in athymic nude mice of markedly decreased numbers and percentages of B cells in perivascular inflammatory cuffs suggests that T cells are required for the subsequent infiltration of B cells during SV encephalitis. The B cells that do enter continue to express primarily IgM, indicating a lack of maturation to the more “mature” isotypes. IA is initially expressed by perivascular mononuclear cells in the brain on day 2 after SV inoculation. Later, it is also expressed by stellate parenchymal cells and perivascular endothelial cells and/or pericytes. In nude mice the expression of IA in all of these cell types is markedly blunted, suggesting that T cells are required for the full expression of IA in the brain.