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

Abstract

Abstract 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 naïve, 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 naïve/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.