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J Neurotrauma. 2019 Sep 1;36(17):2579-2589. doi: 10.1089/neu.2018.6368. Epub 2019 May 23.

Intraparenchymal Application of Mature B Lymphocytes Improves Structural and Functional Outcome after Contusion Traumatic Brain Injury.

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Vaccine and Immunotherapy Center, Department of Medicine, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Neuroscience Center, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.


Cerebral contusion causes neurological dysfunction mediated in part by inflammatory responses to injury. B lymphocytes are dynamic regulators of the immune system that have not been systematically studied in traumatic brain injury (TBI). We showed previously that topically applied mature B cells have immunomodulatory properties and strongly promote tissue regeneration, including cutaneous nerve growth, in acute and chronic skin wounds. Using a mouse controlled cortical impact (CCI) model, we assessed a possible beneficial role of exogenously applied B cells on histopathological and functional outcome after TBI. Mice were injected intraparenchymally at the lesion site with 2 × 106 mature naïve syngeneic splenic B cells, then subjected to CCI. Control CCI mice received equal numbers of T cells or saline, and sham-injured mice (craniotomy only) were given B cells or saline. Sham-injured groups performed similarly in motor and learning tests. Injured mice administered B cells showed significantly improved post-injury rotarod, Y maze, and Morris water maze (MWM) performance compared with saline- or T-cell-treated CCI groups. Moreover, lesion volume in mice treated with B cells was significantly reduced by 40% at 35 days post-TBI compared with saline and T cell controls, and astrogliosis and microglial activation were decreased. In vivo tracking of exogenous B cells showed that they have a limited life span of approximately 14 days in situ and do not appear to proliferate. The data suggest proof of principle that local administration of B lymphocytes may represent a therapeutic option for treatment of cerebral contusion, especially when clinical management involves procedures that allow access to the injury site.


B cells; CCI; TBI; inflammation; learning and memory; lymphocytes


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