B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice.
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.
Ankeny
Daniel P
DP
Center for Brain and Spinal Cord Repair, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University Medical Center, 460 West 12th Avenue, Columbus, OH 43210-1239, USA.
Guan
Zhen
Z
Popovich
Phillip G
PG
D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001522:Behavior, Animal / Q000502:physiology; D015922:Complement C1q / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009416:Nerve Regeneration / Q000276:immunology*; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology; D020127:Recovery of Function / Q000276:immunology*; D013119:Spinal Cord Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
D001323:Autoantibodies; D007074:Immunoglobulin G; D011961:Receptors, Fc; D015922:Complement C1q