Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis

Magliozzi, Roberta; Columba-Cabezas, Sandra; Serafini, Barbara; Aloisi, Francesca

doi:10.1016/j.jneuroim.2003.10.056

Cited by 286 publications

(236 citation statements)

References 43 publications

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“…Virus-specific ASC are detected in the lymphoid tissues prior to the CNS [16], similar to findings for T cells [30]. Consistent with their derivation from secondary lymphoid organ [14,[51][52][53]. Although a small frequency of oligoclonal Ab in the CSF of MS patients are specific for Ag associated with viral infections acquired as young adults, the majority have as-yet-undefined specificities [18].…”

Section: Cns Versus Peripheral Ascmentioning

confidence: 66%

“…Consistent with their derivation from secondary lymphoid organ germinal centers, virus-specific ASC in the CNS emerge subsequent to germinal center reactions, which peak *12 days p.i. [4,6] [51][52][53]. Although a small frequency of oligoclonal Ab in the CSF of MS patients are specific for Ag associated with viral infections acquired as young adults, the majority have as-yet-undefined specificities [18].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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 ASCsupporting environment, even after resolution of viral infection and in the absence of chronic ongoing inflammation. IntroductionThe preeminent goal of the immune system is to eliminate pathogens and establish immunological memory [1]. Both T cells and Ab participate in eliminating a variety of pathogens; however, sustained serum Ab is an important criteria for many vaccination strategies, as they provide the first line of defense against re-infection [2]. Upon Ag encounter in regional lymph nodes, B cells undergo clonal expansion in extrafollicular foci and within germinal centers [3,4].Rapidly activated B cells secrete low-affinity Ab but can undergo isotype switching and limited BCR hypermutation as they differentiate into plasmablasts [3]. In the milieu of accessory cells and cytokines, germinal center B cells undergo affinity maturation and ultimately differentiate into both Ab-secreting cells (ASC) and memory B cells. As Ag is depleted, ASC and memory B cells are detected with increasing frequency in BM [2], where both stromal cells and other resident cells provide soluble as well as contact-dependent survival signals, including CXCL12 and BAFF [5]. Ab secretion by terminally differentiated plasma cells is independent of both Ag and T cell regulation [2,6]. Long-lived ASC in BM and spleen maintain serum Ab, thus providing protective immunity to re-infection, sometimes for the [4,6]. In contrast to Ag encountered in the periphery, the regulation of B cell activation by Ag sequestered within the central nervous system (CNS) is less clear. The absence of dedicated lymphatic drainage and the presence of the blood brain barrier (BBB) limits Ag transport from the CNS into secondary lymphoid tissue as well as trafficking of both cells and macromolecule...

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Section: Cns Versus Peripheral Ascmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…In particular, CCL2, CCL3, CCL5, and CXCL10 seem to play an important role in the recruitment of T cells and macrophages, acting via CCR2, CCR1, CCR5, and CXCR3, respectively. [1][2][3][4][5][6][7][8][9] More recently, CXCL12 and CCL20 have been shown to attract immature dendritic cells to MS lesions, 12 whereas CXCL13 appeared to direct B-cell recruitment into the CNS, 10,11 and CXCL13-deficient mice have a mild, selflimiting form of EAE. 60 In addition to a pro-inflammatory role, chemokines might also have regulatory effects within the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…Th1-type effector cells expressing the chemokine receptors, CCR5 and CXCR3, appear to be recruited into central nervous system (CNS) parenchyma by the chemokines, CCL3, CCL5, and CXCL10, [1][2][3][4][5] whereas CCL2, CCL3, and CCL5 are important in the recruitment of macrophages via interactions with CCR2, CCR1, and CCR5, respectively. 6 -9 Recently, CXCL13 has been linked to B-cell recruitment in MS 10 and EAE, 11 and immature dendritic cells might be attracted to MS lesions in response to CXCL12 and CCL20. 12 Chemokine receptors have also been localized on resident CNS cell types but the role of these receptors is yet to be fully elucidated.…”

mentioning

confidence: 99%

Neuroprotection and Remyelination after Autoimmune Demyelination in Mice that Inducibly Overexpress CXCL1

Omari

Lutz

Santambrogio

et al. 2009

The American Journal of Pathology

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In rodents, the chemokine CXCL1 both induces the proliferation and inhibits the migration of oligodendrocyte precursor cells. We previously reported that in multiple sclerosis, the same chemokine is expressed by hypertrophic astrocytes, which associate with oligodendrocytes that express the receptor CXCR2. To investigate whether chemokines influence repair after autoimmune demyelination, we generated GFAP-rtTA ؋ ␤-Gal-TRE-CXCL1 double-transgenic (Tg) mice that inducibly overexpress CXCL1 under the control of the astrocyte-specific gene, glial fibrillary acidic protein. Experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, was induced in these animals (and controls) by the subcutaneous injection of myelin oligodendrocyte glycoprotein, and after disease onset, CXCL1 production was initiated by the intraperitoneal injection of doxycycline. Double-Tg animals displayed a milder course of disease compared with both single (CXCL1 or glial fibrillary acidic protein)-Tg and wild-type controls. Pathologies were similar in all groups during the acute stage of disease. During the chronic disease phase, both inflammation and demyelination were diminished in double-Tg mice and Wallerian degeneration was markedly decreased. Remyelination was strikingly more prominent in double-Tg mice, together with an apparent increased number of oligodendrocytes. Moreover, cell proliferation, indicated by BrdU incorporation within the central nervous system, was more widespread in the white matter of double-Tg animals. These findings suggest a neuroprotective role for CXCL1 during the course of autoimmune demyelination.

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“…CXCL13 is a chemokine involved in the development and maintenance of secondary lymphoid organs. During inflammatory processes, CXCL13 is also expressed in non-lymphoid tissues, such as the CNS, where it functions as an attractor of B cells [1].…”

Section: Introductionmentioning

confidence: 99%

CXCL13 levels are more increased in cerebrospinal fluid and plasma of patients with acute infectious than in non-infectious diseases of the central nervous system

Ţilea

Voidăzan

Bălaşa

et al. 2017

Revista Romana De Medicina De Laborator

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Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis

Cited by 286 publications

References 43 publications

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

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

Neuroprotection and Remyelination after Autoimmune Demyelination in Mice that Inducibly Overexpress CXCL1

CXCL13 levels are more increased in cerebrospinal fluid and plasma of patients with acute infectious than in non-infectious diseases of the central nervous system

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