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 3

Antibodies, B cells, and plasma cells accumulate in CSF and injured spinal cord.

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Antibodies, B cells, and plasma cells accumulate in CSF and injured spin...
(A) In contrast to WT mice, BCKO mice fail to produce intrathecal antibodies (ELISA analysis of CSF from n = 8 WT and BCKO mice). (B and C) Quantitation of intraspinal B cell accumulation at 28 dpi (B) and the proportional (prop.) area of IgG staining as a function of time after SCI (C) at the injury site in BL/6 (WT), BALB/c, C57BL/10 (BL10), and B10.PL mice. The intraspinal accumulation of B cells and antibodies is not strain specific, only the magnitude varies; n = 4–8 mice/strain; each bar in B represents the average total number of B220+ lymphocyte profiles in 3 equally spaced sections (1/20th series) spanning 600 μm and centered at the epicenter. (D) Representative sections from uninjured BL/6, SCI BCKO (spinal cord circumscribed by dotted line), and WT mice (42 dpi) reveal the distribution of endogenous antibodies and the specificity of IgG labeling quantified in C, i.e., no labeling exists in spinal cord of uninjured or BCKO mice. (E) Flattened confocal z-stack image reveals accumulation of endogenous antibodies (green, Ig) and Ig+ B cells in the injured spinal cord (42 dpi, individual color channels shown below). bv, blood vessel. (F) Flattened z-stack image with x,y,z-projections showing B220– plasma cells with IgG+ cytoplasm (arrows) nearby but distinct from IgG+B220+ B cells (arrowheads). Scale bars: 200 μm (D); 50 μm (E, top panel); 100 μm (E, bottom panels); 20 μm (F). ***P < 0.001, **P < 0.01 2-way ANOVA with Bonferroni post-test: *P < 0.05, 1-way ANOVA with Tukey’s post-test.