B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice

Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J.M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+ (hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain.

Original languageEnglish
Pages (from-to)4983-4993
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Mar 3 2020

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. The authors acknowledge Drs. Abhijit Budge, Shanrong Zhang, and Shari Birnbaum for their technical expertise for imaging and behavioral analyses and data acquisition. The authors also acknowledge UT Southwestern’s Flow Cytometry Core, the Moody Foundation Flow Cytometry Facility at the Children’s Research Institution, the Advanced Imaging Research Center (Shared Instrumental Grant NIH1S10OD023552-01), Rodent Behavior Core Facility, the Whole Brain Microscopy Facility, and the Neuro-Models Facility with Laura Ingle. This study was funded by grants to A.M.S. from the American Heart Association (14SDG18410020), NIH/NINDS (NS088555), the Dana Foundation David Mahoney Neuroimaging Program, and The Haggerty Center for Brain Injury and Repair (UTSW); to S.B.O. from the American Heart Association (14POST20480373) and NIH/NINDS (3R01NS088555-03S1); to V.O.T. from the NIH/NIAID (5T32AI005284-40) and NIH/NINDS (3R01NS088555-02S1); to U.M.S. from the American Heart Association (17PRE33660147); and to A.J.E. from the NIH (DA023701, DA023555, MH107945) and the US National Aeronautics and Space Administration (NNX15AE09G). S.E.L. and C.W.W. were funded by an NIH institutional training grant (DA007290, Basic Science Training Program in the Drug Abuse Research, Principal Investigator A.J.E.). The UT Southwestern Whole Brain Microscopy Facility and the Neuro-Models Facility are supported by the Texas Institute for Brain Injury and Repair (TIBIR).

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.


  • Adaptive immunity
  • B lymphocytes
  • Focal stroke
  • Neurogenesis
  • Serial two-photon tomography

ASJC Scopus subject areas

  • General


Dive into the research topics of 'B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice'. Together they form a unique fingerprint.

Cite this