B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice
Daniel P. Ankeny, Zhen Guan, Phillip G. Popovich
Daniel P. Ankeny, Zhen Guan, Phillip G. Popovich
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Research Article

B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice

Abstract

Traumatic injury to the mammalian spinal cord activates B cells, which culminates in the synthesis of autoantibodies. The functional significance of this immune response is unclear. Here, we show that locomotor recovery was improved and lesion pathology was reduced after spinal cord injury (SCI) in mice lacking B cells. After SCI, antibody-secreting B cells and Igs were present in the cerebrospinal fluid and/or injured spinal cord of WT mice but not mice lacking B cells. In mice with normal B cell function, large deposits of antibody and complement component 1q (C1q) accumulated at sites of axon pathology and demyelination. Antibodies produced after SCI caused pathology, in part by activating intraspinal complement and cells bearing Fc receptors. These data indicate that B cells, through the production of antibodies, affect pathology in SCI. One or more components of this pathologic immune response could be considered as novel therapeutic targets for minimizing tissue injury and/or promoting repair after SCI.

Authors

Daniel P. Ankeny, Zhen Guan, Phillip G. Popovich

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Figure 2

Significant neuroprotection is evident in the injured spinal cord of BCKO mice at 63 dpi.

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Significant neuroprotection is evident in the injured spinal cord of BCK...
The total lesion volume (A) is reduced in BCKO mice and is accompanied by marked sparing of spinal cord (SC) gray matter (GM) (B), and white matter (WM) (C). Volumes were estimated using Cavalieri’s method. (D and E) 3D reconstructions of spinal cords taken from animals with total lesion volume that is closest to the average for each group. Gray indicates spared white matter (SWM; regions containing myelin and axon profiles that are morphologically normal); green indicates spared gray matter (SGM); red indicates frank lesion (complete loss of normal cytoarchitecture); and yellow indicates lesioned white matter (regions where axons and myelin are absent). Coronal slabs are sampled at 0.8-mm caudal to the injury epicenter and are marked by dashes in the complete 3D reconstructions. C, caudal; R, rostral. Immunofluorescent double labeling of spared white matter 1.6-mm caudal to the injury epicenter from a WT (F) and BCKO mouse (G) reveals increased sparing of axons (green, anti-NFH) and myelin (red, anti-MBP) in BCKO mice. Dotted line delineates gray matter–white matter interface. Blue (DAPI) staining in merged image reveals cell nuclei. Cartoon in top right panel depicts imaged region. Scale bar: 0.5 mm (D and E); 40 μm (F and G). *P < 0.05, **P < 0.01, ***P < 0.001 versus WT; 2-tailed t tests. All data was collected at 63 dpi.