Chemotactic Responsiveness Toward Ligands for CXCR3 and CXCR4 Is Regulated on Plasma Blasts During the Time Course of a Memory Immune Response

Hauser, Anja E.; Debes, Gudrun F.; Arce, Sergio; Cassese, Giuliana; Hamann, Alf; Radbruch, Andreas; Manz, Rudolf A.

doi:10.4049/jimmunol.169.3.1277

Cited by 320 publications

(363 citation statements)

References 40 publications

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“…Indeed, the responsiveness of chemokine receptors for their respective ligands is differentially regulated (e.g., by RGS proteins) during the orchestration of the migration of lymphoid subpopulations into anatomic compartments, their development, activation, and immune response (26,27,(31)(32)(33)(34)(35)(36). B cells from different developmental stages, e.g., developing bone marrow B cells (36), B cells leaving GC structures (33), and medullary plasmablasts leaving lymph nodes (34), have been found to express high levels of surface CXCR4 but were unresponsive to CXCL12.…”

Section: Discussionmentioning

confidence: 99%

“…CDϩ peripheral blood B cells were enriched by positive immunomagnetic separation (Miltenyi Biotec, Bergisch Gladbach, Germany) and subsequently incubated overnight at 37°C under 5% CO 2 -buffered conditions in RPMI 1640 medium (Biochrom, Berlin, Germany) supplemented with 2 mM L-glutamine, 10% fetal calf serum, 25 mg/ml penicillin/streptomycin, and 1 g/ml lipopolysaccharide (LPS) (from Escherichia coli; Sigma). Subsequently, cell migration was examined in wells containing transwell inserts (Costar, Bodenheim, Germany) with a 6.5-mm diameter and 5-m pores using fibronectin (Invitrogen, Karlsruhe, Germany)-precoated membranes, as previously described (26,27). Briefly, 5 ϫ 10 5 B cells per upper well were suspended in RPMI 1640 medium supplemented with 0.5% BSA (Sigma) and then incubated for 90 minutes at 37°C under 5% CO 2 -buffered conditions.…”

Section: Methodsmentioning

confidence: 99%

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Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome

Hansen¹,

Reiter²,

Ziprian³

et al. 2005

Arthritis & Rheumatism

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Objective. To assess whether abnormal chemokine receptor expression and/or abnormal responsiveness to the cognate ligands might underlie some of the disturbances in B cell homeostasis characteristic of primary Sjögren's syndrome (SS).Methods. Chemokine receptor expression by CD27؊ naive and CD27؉ memory B cells from patients with primary SS and healthy control subjects was analyzed using flow cytometry, single-cell reverse transcriptase-polymerase chain reaction (RT-PCR), and migration assays.Results. In contrast to healthy subjects, significantly higher expression of both surface CXCR4 and CXCR4 messenger RNA (mRNA) was seen in peripheral blood B cells from patients with primary SS. These differences were most prominent in CD27؊ naive B cells (P < 0.0006). In addition, significantly higher frequencies of CD27؊ naive B cells from patients with primary SS expressed mRNA for the inhibitory regulator of G protein signaling 13 (P ‫؍‬ 0

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome

Hansen¹,

Reiter²,

Ziprian³

et al. 2005

Arthritis & Rheumatism

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“…Outside of this time window, only few plasmablasts and plasma cells are detectable in blood, and most if not all of them are obviously derived from mucosal immune responses 48. In mice, as early as 2 weeks after their generation, plasma cells have lost their mobility, they do not move within the bone marrow,42 and when isolated from the bone marrow, they do not migrate toward gradients of CXCL12 in transwell migration assays 14. This is even more surprising, since they still express CXCR4, and react to CXCL12 by improved survival in tissue culture 7.…”

Section: Conditional Survival Of Memory Plasma Cells—the Memory Nichementioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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“…Migration of plasmablasts into inflamed tissues frequently correlates with CXCL10 expression [40][41][42]. Transient responsiveness to the CXCR3 ligands CXCL9, 10 and 11 has also been shown to mediate plasmablast migration in vitro [40].…”

Section: Cns Asc Retentionmentioning

confidence: 99%

“…Nevertheless, decreasing class II surface expression on CD138 + pre-plasma cells supports ongoing differentiation for at least a 2-month period. These data suggest that plasmablasts are recruited into the CNS at early stages of differentiation from secondary lymphoid organs.Migration of plasmablasts into inflamed tissues frequently correlates with CXCL10 expression [40][41][42]. Transient responsiveness to the CXCR3 ligands CXCL9, 10 and 11 has also been shown to mediate plasmablast migration in vitro [40].…”

mentioning

confidence: 99%

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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Chemotactic Responsiveness Toward Ligands for CXCR3 and CXCR4 Is Regulated on Plasma Blasts During the Time Course of a Memory Immune Response

Cited by 320 publications

References 40 publications

Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome

Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome

Immunological memories of the bone marrow

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

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