A functional BCR in human IgA and IgM plasma cells

Pinto, Dora; Montani, Erica; Bolli, Martin; Garavaglia, Guido; Sallusto, Federica; Lanzavecchia, Antonio; Jarrossay, David

doi:10.1182/blood-2012-09-459289

Cited by 120 publications

(125 citation statements)

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“…Under these conditions, a significant fraction of the cells differentiated within 6 days into Ig-secreting CD138 + plasma cells [20,41,42]. B-cell maturation was followed by monitoring CD138 expression and icIgM ( Fig.…”

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

confidence: 99%

“…The rare peripheral blood plasma cells are characterized by high expression of CD27 and CD38, Ig secretion, and an increasing presence of CD138 [17]. Isolated plasma cells die within 3 days by apoptosis, but using BM-derived stromal cells as feeder cells remarkably improves plasma cell survival [18][19][20]. In agreement with this in vitro observation, it was shown that in vivo plasma cells, which express VLA-4 and CXCR4, in the BM colocalize with stromal cells expressing VCAM-1 and CXCL12 and may require additional survival factors [17,20,21].…”

Section: Introductionmentioning

confidence: 99%

“…Isolated plasma cells die within 3 days by apoptosis, but using BM-derived stromal cells as feeder cells remarkably improves plasma cell survival [18][19][20]. In agreement with this in vitro observation, it was shown that in vivo plasma cells, which express VLA-4 and CXCR4, in the BM colocalize with stromal cells expressing VCAM-1 and CXCL12 and may require additional survival factors [17,20,21].It was thought that CXCR4 and its ligand CXCL12 represent a unique couple [22], but this view changed when it was shown that CXCL12 can bind and partially signal through CXCR7 [23][24][25]. Expression of CXCR7 mRNA in leukocytes is amply reported [24,26].…”

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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 Plasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…A similar observation was previously reported for antibody-secreting cells in the human gut 8 and for plasma cells. 9 To further examine surface IgA on LLPCs, we turned to a mucosal disease that affects nearly all children, namely, rotavirus. During the first years of life, nearly all children will experience a rotavirus infection at least once.…”

Section: Resultsmentioning

confidence: 99%

Long-lived plasma cells in human bone marrow can be either CD19+ or CD19–

et al. 2017

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“…IgA is not an inflammatory cytokine, but it plays an important role in intestinal mucosal immunity system by mediating humoral immunity. IgA is regulated by the nervous system, endocrine system and immune system, but IgA is released by plasma cells and has a vital role in intestinal mucosa immunity (Brandtzaeg, 2010;Pinto et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Effect of Visfatin on the Structure and Immune Levels in the Small Intestine of LPS-Induced Rats

Zhou

Yuan

et al. 2015

Int. J. Morphol.

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SUMMARY:This study investigated the effects of visfatin on the structure and the immunity levels in the small intestine of LPS-induced rats. Forty Wistar male and female SPF rats were randomly and equally divided into four groups: the saline (control), vistfatin, lipopolysaccharide (LPS), and visfatin+LPS co-stimulated. The functions of visfatin in the intestinal mucosal immunity were investigated by examining the variation of tissue structure, inflammation and immunity-related proteins in the intestine of immunologically stressed rats using HE staining, ELISA, immunohistochemistry and Western Blot. The results showed that, when compared with the control group, the visfatin-treated group showed a decrease in the intestinal villus height and width, and a significant increase in the levels of IL-6 and TNF-∂ as well as Immunoglobulin A (IgA) positive cells. Additionally, when compared with the LPS-treated group, the visfatin+LPS co-stimulated group showed a decrease in the villus height and width as well as the levels of IL-6 and TNF-∂, and an increase in IgA levels, implying a shrinking response to LPS injection. All the results suggest that, under normal physiological conditions, visfatin disturbs the body's homeostasis and causes intestinal villus atrophy by increasing IgA expression. While under immune response conditions, LPS acts as an exogenous antigen to promote visfatin against LPS-induced inflammation by decreasing the expression of IgA. Under immune stress conditions, visfatin as an exogenous stimulus promotes the immune response by regulating the protein levels of IL-6, TNF-∂ and IgA.

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A functional BCR in human IgA and IgM plasma cells

Abstract: Key Points IgA and IgM human plasma cells express a functional BCR on their cell surface and can therefore respond to antigenic stimulation.

Cited by 120 publications

References 20 publications

CXCR7 influences the migration of B cells during maturation

CXCR7 influences the migration of B cells during maturation

Long-lived plasma cells in human bone marrow can be either CD19+ or CD19–

Effect of Visfatin on the Structure and Immune Levels in the Small Intestine of LPS-Induced Rats

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