CNS viral infection diverts homing of antibody-secreting cells from lymphoid organs to the CNS

Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
European Journal of Immunology (Impact Factor: 4.03). 04/2006; 36(3):603-12. DOI: 10.1002/eji.200535123
Source: PubMed


Neurotropic coronavirus infection of mice results in acute encephalomyelitis followed by viral persistence. Whereas cellular immunity controls acute infection, humoral immunity regulates central nervous system (CNS) persistence. Maintenance of serum Ab was correlated with tissue distribution of virus-specific Ab-secreting cells (ASC). Although virus-specific ASC declined in cervical lymph node and spleen after infectious virus clearance, virus-specific serum Ab was sustained at steady levels, with a delay in neutralizing Ab. Virus-specific ASC within the CNS peaked rapidly 1 wk after control of infectious virus and were retained throughout chronic infection, consistent with intrathecal Ab synthesis. Surprisingly, frequencies of ASC in the BM remained low and only increased gradually. Nevertheless, virus-specific ASC induced by peripheral infection localized to both spleen and BM. The data suggest that CNS infection provides strong stimuli to recruit ASC into the inflamed tissue through sustained up-regulation of the CXCR3 ligands CXCL9 and CXCL10. Irrespective of Ag deprivation, CNS retention of ASC coincided with elevated BAFF expression and ongoing differentiation of class II+ to class II-CD138+CD19+ plasmablasts. These results confirm the CNS as a major ASC-supporting environment, even after resolution of viral infection and in the absence of chronic ongoing inflammation.

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    • "Notably, CCL5 neutralization abrogates both CD4þ and CD8þ T cell accumulation during chronic infection (Glass et al., 2004), indicating differential chemokine usage between the T cell subsets (Stiles et al., 2009). More recently, Bergmann and colleagues have provided compelling evidence that CXCR3 ligands CXCL9 and CXCL10 are crucial for allowing plasmablast migration into the CNS of MHV-infected mice via signaling through CXCR3 expressed on these cells (Marques et al., 2011; Phares et al., 2011; Tschen et al., 2006). These findings highlight a previously unappreciated role for these chemokines in host defense by attracting activated antibody secreting cells into the CNS of mice persistently infected with a neurotropic virus. "
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    • "The trafficking and persistence of ASC in the CNS also occurs in other viral models. We observed that antiviral IgM and IgG ASC in the spleen preceded the detection of ASC in the brain, suggesting that B cells from the periphery are activated and subsequently traffic to the CNS where they differentiate into ASC, as occurs for mouse hepatitis virus [29]. Similar to our results, virus-specific ASC are detected in mouse brains for one year after infection with Sindbis virus [30] and for 90 days after infection with mouse hepatitis virus [29,31]. "
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    • "By comparison to other viral encephalitis models, CXCL13 was not induced in the CNS during experimental coronavirus encephalomyelitis despite prominent accumulation of virus-specific antibody-secreting cells in the target tissue (Tschen et al., 2006). Here, CXCL9 and CXCL10, both acting on plasmablasts through CXCR3, were implicated in CNS B cell recruitment (Tschen et al., 2006). Our data would suggest that neither CXCL9 nor CXCL10 are likely responsible for B cell recruitment to the CNS of SVinfected animals, since one mediator (CXCL9) is simply not induced by infection and the other (CXCL10) only goes up transiently and then declines as B cell influx begins in earnest (Fig. 1C and 1D). "
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