Recruitment of GL7+ B cells to the inflamed CNS prior to peripheral germinal center formation (VIR1P.1151)

Central nervous system (CNS) inflammation induced by viral infection and autoimmune disease results in the accumulation of various B cell subsets, including antibody secreting cells (ASC). However, temporal dynamics and precursor relationships of B cell subsets between the periphery and the inflamed CNS remain unclear. Encephalomyelitis induced by gliatropic coronavirus JHMV resolves into a persistent CNS infection that is controlled by local humoral immunity. Prior to the accumulation of essential CD138+ ASC, CD138- B cells traffic to the CNS by day 5 post infection (p.i.). Analysis of these early accumulating B cells by flow cytometry shows they comprise several phenotypes, which typically reside within the cervical lymph node (CLN), including naive, activated, germinal center (GC)-like (GL7+), and unswitched memory B cells. B cell activation within the CLN occurs by day 7 p.i., but GC formation is not robust until day 14 p.i.. Unexpectedly, GL7+ B cells are detected within the CNS prior to GC formation. Moreover, in contrast to naive/early activated B cells, which decline in number, GL7+ B cells increase differentially in brain and spinal cord throughout persistence. Maintenance of more differentiated B cell subsets within the CNS suggests either selective ongoing recruitment from the periphery or preferential local CNS maintenance. The lack of evidence for ectopic follicles suggests activated B cells, including GC-like B cells, can be recruited from the CLN.