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
Published September 21, 2009
Citation Information: J Clin Invest. 2009;119(10):2990-2999. https://doi.org/10.1172/JCI39780.
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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 6

IgG and complement C1q colocalize in regions of pathology in spinal cord of WT mice.

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IgG and complement C1q colocalize in regions of pathology in spinal cord...
(A and C) Confocal microscopy reveals a relationship among axons (green, anti–200-kDa NFH), Igs (red, anti-mouse Ig), and complement C1q (blue, anti-C1q) in the ventrolateral funiculus at a site and rostral (1.6 mm) to a site of SCI in WT mice. (B and D) In BCKO mice, sparse Ig and C1q labeling can be seen among markedly preserved axon tracts and gray matter. (E) Colocalization of IgG (green) and C1q on cells with glial morphology in the lateral funiculus approximately 400-μm caudal to the epicenter. (F) x/y/z-projections of a flattened z-stack image from a section adjacent to site of injury, showing IgG and NFH colocalization in the ventral horn, on a cell with motor neuron morphology (center): single channel images are depicted below. Scale bars: 100 μm (A–D); 50 μm (E and F).