Development and Migration of Plasma Cells in the Mouse Lymph Node

Fooksman, David R.; Schwickert, Tanja A.; Victora, Gabriel D.; Dustin, Michael L.; Nussenzweig, Michel C.; Skokos, Dimitris

doi:10.1016/j.immuni.2010.06.015

Cited by 130 publications

(160 citation statements)

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“…2B) during 6 days of culture revealed an interesting inverse correlation between CXCR7 and CXCR5 surface levels. On the increasing cell population, which contained high levels of icIgM, CXCR5 was initially weakly expressed and gradually disappeared during maturation, consistent with the notion that when the master transcription factor of plasma cell differentiation Blimp1 is activated, CXCR5 becomes downregulated [44].…”

Section: Cxcr7 Is Differentially Expressed On Memory B Cells and Plassupporting

confidence: 82%

“…3). Advancing maturation, the downregulation of CXCR7 on plasma cells is in agreement with their gain in responsiveness to CXCL12 at the medullary cords shown in vivo, which is essential for homing to the BM in order to become long-lived plasma cells [14,44,54]. The observation that CXCR7 is particularly abundant on the surface of CD27 + CD38 + CXCR5 − B cells falls into the paradigm of cell stage specific chemokine receptor expression.…”

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

“…The movement of plasmablasts from the GCs to the distant medulla is random and independent of a chemotactic system. Thus, plasmablasts leave follicles and reach, most likely by stochastic migration, the medullary cords where they differentiate into plasma cells [2,44,50].Contrary to CCR7 and CXCR5, CXCR4 is found to be expressed on almost all B-cell stages and is critical for homing of long-lived plasma cells [14]. Expression of CXCR4 was shown to be increased on GC B cells, but at the same time being heterogeneous.…”

mentioning

confidence: 99%

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CXCR7 influences the migration of B cells during maturation

Humpert

Pinto²,

Jarrossay³

et al. 2014

Eur J Immunol

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The atypical chemokine receptor CXCR7 binds the chemokines CXCL12 and CXCL11. The receptor is widely expressed and was shown to tune CXCR12-induced responses of CXCR4. Here, the function of CXCR7 was examined at late stages of human B-cell maturation, when B cells differentiate into Ab-secreting plasmablasts. We identified two populations of CXCR7 + cells in tonsillar lymphocytes, one being presumably memory potential contribution of the scavenger receptor in final B-cell maturation. On in vitro differentiating B cells, we found a marked inverse correlation between CXCR7 and CXCR5 cell surface levels, whereas expression of CXCR4 remained almost constant. Migration assays performed with tonsillar mononuclear cells or in vitro differentiated cells revealed that inhibition of CXCR7 markedly increases chemotaxis toward CXCL12, especially at late stages of B-cell maturation. Chemotaxis was attenuated in the presence of CXCR4 antagonists, confirming that migration is CXCR4 mediated. Our findings unequivocally demonstrate a novel role for CXCR7 in regulating the migration of plasmablasts during B-cell maturation.Keywords: Atypical chemokine receptor r B cells r CXCR4 r CXCR5 r CXCR7Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAfter birth, B lymphopoiesis occurs in the BM, where cells progress through pro-B cell and pre-B cell stages. By expression of a functional BCR, B cells acquire antigen specificity and enter the periphery as transitional immature B cells, eventually maturing into follicular or marginal zone B cells [1]. Follicular B cells circulateCorrespondence: Dr. Marcus Thelen e-mail: marcus.thelen@irb.usi.ch between lymphoid organs and form GCs within secondary lymphoid organs upon activation. The GC splits up into two histological distinct compartments, the dark zone, where B cells are tightly packed and proliferate, and the light zone. Within the GC, CXCL12 is preferentially expressed in the dark zone, whereas CXCL13, which is also expressed in the follicle, is mainly found in the light zone. B cells may modulate the surface expression of CXCR5 and move between the zones of the GC attracted by CXCL12 and CXCL13 [2]. Activated B cells can grow and differentiate into plasmablasts in extrafollicular foci or form GCs within follicles [3,4]. Within the GC, activated B cells can differentiate into memory or plasma C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 694-705 Cellular immune response 695 cells [5]. Cells expressing a BCR with high avidity for an antigen differentiate preferentially along the plasma cell pathway and this process might be regulated by expression of factors such as the B-lymphocyte maturation-induced-protein-1, BCL-6, and X-box binding protein-1 [6][7][8] or cytokines such as IL-6 or APRIL [3]. Others showed that Bcl-2, the cytokine IL-21, and SWAP-70, which functions in activation, homing, and class switching of B cells, and is strongly upregulated in GC B cel...

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Section: Cxcr7 Is Differentially Expressed On Memory B Cells and Plassupporting

confidence: 82%

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

CXCR7 influences the migration of B cells during maturation

Humpert

Pinto²,

Jarrossay³

et al. 2014

Eur J Immunol

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“…One of the central questions in this field is whether migration is best described as a (persistent) random walk or whether directed or confined migration is involved, because this is important for our understanding of how cells manage to carry out their functions. Examples of persistent random walk include the migration of T cells, B cells, and plasma cells in lymph nodes (2,(6)(7)(8) and of effector T cells migrating in tumors (9), whereas nonrandom migration has for instance been discovered in antigen-engaged B cells moving toward the T zone boundary early in a B-cell response (10), CD8 + T cells being attracted toward "licensed" dendritic cells (11)(12)(13)(14), neutrophil movement in skin (15,16), and during thymocyte maturation (17,18).…”

mentioning

confidence: 99%

B cells within germinal centers migrate preferentially from dark to light zone

Beltman

Allen

Cyster

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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One of the main questions in the field of imaging immune cell migration in living tissues is whether cells fulfill their functionality via random or nonrandom migration processes. For some applications, this issue has remained controversial even after publication of various imaging studies. A prime example is B-cell migration in germinal centers (GCs) where somatic hypermutation and clonal selection of B cells are thought to occur within morphologically distinct regions termed dark zone (DZ) and light zone (LZ). Here, we reanalyze a previously published dataset on GC B-cell migration, applying a sensitive analysis technique to detect directed migration and using a procedure to correct for a number of artifacts that frequently occur in time-lapse imaging experiments. Although B cells roughly perform a persistent random walk, we present evidence that they have a small preference (of on average about 0.2−0.3 μm min −1 ) to migrate from DZ to LZ, which is consistent with classical views of the GC reaction. This preference is most pronounced among a large subset of almost half of the B-cell population migrating along relatively straight tracks. Using a computational model to generate long-lasting B-cell tracks based on the experimental motility data (including the small directional preference), we predict a time course to travel from DZ to LZ of a few hours. This is consistent with experimental observations, and we show that at the observed cellular motility such a time course cannot be explained without the small preferential migration from DZ to LZ.B-cell motility | cyclic reentry | two-photon microscopy T hanks to the application of two-photon microscopy to living lymphoid tissues, an exciting glimpse of how the migration of various types of immune cells takes place was recently obtained (1-5). One of the central questions in this field is whether migration is best described as a (persistent) random walk or whether directed or confined migration is involved, because this is important for our understanding of how cells manage to carry out their functions. Examples of persistent random walk include the migration of T cells, B cells, and plasma cells in lymph nodes (2, 6-8) and of effector T cells migrating in tumors (9), whereas nonrandom migration has for instance been discovered in antigen-engaged B cells moving toward the T zone boundary early in a B-cell response (10), CD8 + T cells being attracted toward "licensed" dendritic cells (11)(12)(13)(14), neutrophil movement in skin (15, 16), and during thymocyte maturation (17,18).In some applications, it is controversial whether migration is best described as random or not, and a prime example is B-cell migration in germinal centers (GCs). At these sites, B lymphocytes mature by somatic hypermutation and clonal selection of the mutants that produce antibody of high affinity. These two processes are thought to occur in morphologically distinct regions termed dark zone (DZ) and light zone (LZ), but in the literature competing views exist on the functional meaning of D...

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