The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system

Brain Behav Immun. 2011 Jul;25(5):922-31. doi: 10.1016/j.bbi.2010.10.002. Epub 2010 Oct 8.


Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / immunology*
  • Alphavirus Infections / physiopathology
  • Animals
  • Astrocytes / immunology
  • Astrocytes / virology
  • B-Lymphocytes / physiology*
  • Brain / immunology
  • Brain / virology
  • Cells, Cultured
  • Chemokine CXCL13 / physiology*
  • Chemotaxis, Leukocyte / physiology*
  • Encephalitis, Viral / immunology*
  • Encephalitis, Viral / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Flow Cytometry
  • Mice
  • Mice, Inbred C57BL
  • Microglia / immunology
  • Microglia / virology
  • Polymerase Chain Reaction
  • Sindbis Virus / immunology*
  • Th1 Cells / immunology
  • Th1 Cells / physiology
  • Th17 Cells / immunology
  • Th17 Cells / physiology


  • Chemokine CXCL13
  • Cxcl13 protein, mouse