The kinetics of B-cell trafficking and long-term maintenance in the CNS induced by Sindbis virus infection (39.14)

Abstract

Abstract Anti-viral antibodies are essential for both the clearance of Sindbis virus (SINV) and long-term suppression of reactivation in the CNS. To characterize the changing functional characteristics of B-cells and identify important determinants of B-cell trafficking and long-term maintenance, CNS tissue from SINV-infected mice was assessed at various times post-infection (pi) using flow cytometry and qRT-PCR. Plasmablasts (PBs) and memory B-cells (MBs) (CD19+CD38+CD138-IgM-IgD-) were 70% of the B-cell population for at least 6-mo pi, while plasma cells (CD19+/-CD38-CD138-) were less than 5% of the population. Staining for intracellular and surface IgG at day 26 pi detected 50% PBs and 60% MBs. A small population of CD19+CD38-CD138- cells was detected indicating possible germinal center (GC) B-cells in the brain. Further staining for GC marker GL-7 detected GL-7+ CD38+/- cells in the brain for at least 1-mo pi. mRNA levels of CXCL9/CXCL10 (trafficking), CCL19/CXCL13 (follicle formation), and BAFF (B-cell survival) peaked on days 5-7 pi. Levels gradually decreased and returned close to baseline by 6-mo pi except for BAFF that was maintained at a low level. The expression of CXCR3, CCR7, and BAFF receptor were detected on B-cells for at least 1-mo pi. These results suggest that PBs and MBs play a role in the long-term suppression of SINV replication and that the brain may provide a microenvironment for differentiation and survival of B-cells.