Project Summary

Upon cerebral ischemia, an inflammatory reaction mediated by infiltrating immune cell subsets as well as
activation of resident microglia cells has been shown to have both beneficial and detrimental effects on
stroke outcome. We have found that in the chronic phase of stroke, B cells start to cluster with CD4+ T
cells and myeloid cells and differentiate into plasma cells within ectopic lymphoid structures (ELS) in the
ischemic brain. The observation that post-stroke cognitive decline was associated with the occurrence of
brain-infiltrating B cells and CNS antigen-specific antibodies in stroke patients and could be prevented by B
cell depletion in a mouse model of stroke, strongly suggests a pathophysiological role of CNS-directed
humoral immune responses after stroke. Here, we hypothesize that activated microglia and infiltrating
monocytes/macrophages together with infiltrating lymphocytes are essential for the induction and
differentiation of lymphoid tissue-like PDGFRβ+ stromal cells, which in turn provide important cues for the
recruitment, activation and differentiation of B cells within ELS in the ischemic brain. A better understanding
of the crosstalk between myeloid cells, lymphocytes and stromal cells in establishing and maintaining ectopic
lymphoid structures in the ischemic brain might contribute to the discovery of a causal treatment of poststroke
cognitive decline.