scholarly journals The G protein–coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination

2015 ◽  
Vol 212 (13) ◽  
pp. 2213-2222 ◽  
Author(s):  
Jagan R. Muppidi ◽  
Erick Lu ◽  
Jason G. Cyster
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Follicular Dendritic Cell ◽  
Dependent Manner ◽  
Downstream Effector ◽  
Cell Clustering ◽  
Cell Association ◽  
Sphingosine 1 Phosphate ◽  
Follicular Dendritic

The orphan Gα13-coupled receptor P2RY8 is mutated in human germinal center (GC)–derived lymphomas and was recently found to promote B cell association with GCs in a mouse model. Here we establish that P2RY8 promotes clustering of activated B cells within follicles in a follicular dendritic cell (FDC)–dependent manner. Although mice lack a P2RY8 orthologue, we show that mouse GC B cell clustering is also dependent on FDCs acting to support the function of a Gα13-coupled receptor. Mutations in GNA13 and its downstream effector ARHGEF1 are associated with the development of disseminated GC-derived lymphomas. We find that egress of Gna13 mutant GC B cells from lymph nodes in the mouse depends on sphingosine-1-phosphate receptor-3. These findings provide evidence that FDCs promote GC confinement of both human and mouse GC B cells via Gα13-dependent pathways, and they show that dissemination of Gα13-deficient GC B cells additionally requires an egress-promoting receptor.

scholarly journals Identification of a Human Follicular Dendritic Cell Molecule That Stimulates Germinal Center B Cell Growth

2000 ◽  
Vol 191 (6) ◽  
pp. 1077-1084 ◽  
Author(s):  
Li Li ◽  
Xin Zhang ◽  
Sharlotte Kovacic ◽  
Andrew J. Long ◽  
Karen Bourque ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Growth ◽  
B Cell ◽  
Germinal Center ◽  
Cell Cycle Progression ◽  
Follicular Dendritic Cell ◽  
Cd40 Ligand ◽  
Signal Molecule ◽  
Germinal Center B Cell ◽  
Follicular Dendritic

The initial interaction between B cells and follicular dendritic cells (FDCs) appears to be essential for germinal center (GC) formation. To identify molecules regulating this interaction, we generated FDC-staining monoclonal antibodies (mAbs) and screened them for their ability to block FDC-mediated costimulation of growth and differentiation of CD40-stimulated B cells. Using one of the inhibitory mAbs, 8D6, we expression cloned the cDNA encoding the 8D6 antigen (Ag) from a human FDC line, HK. The 8D6 Ag is a novel protein of 282 amino acids that is expressed abundantly on FDCs. Monolayers of COS cells transiently transfected with the 8D6 Ag cDNA stimulate B cell growth. The mAb 8D6 blocks the costimulatory function completely. The inhibitory activity of the mAb 8D6 was demonstrated to be due to an inhibition of cell cycle progression of CD40 ligand–stimulated GC B cells. In addition, the mAb 8D6 inhibits the growth of a lymphoma of GC origin, L3055, which depends on FDCs or HK cells for its growth. These findings suggest that the primary function of FDCs in the GC is to stimulate B cell growth. An FDC signal molecule, 8D6 Ag, may be an important molecule to mediate this function.

scholarly journals Normal Induction but Attenuated Progression of Germinal Center Responses in BAFF and BAFF-R Signaling–Deficient Mice

2003 ◽  
Vol 198 (8) ◽  
pp. 1157-1169 ◽  
Author(s):  
Ziaur SM. Rahman ◽  
Sambasiva P. Rao ◽  
Susan L. Kalled ◽  
Tim Manser
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Fate ◽  
Germinal Center ◽  
Antigen Expression ◽  
Follicular Dendritic Cell ◽  
Current Data ◽  
B Cell Survival ◽  
Survival And Development ◽  
Contrast Analysis

The factors regulating germinal center (GC) B cell fate are poorly understood. Recent studies have defined a crucial role for the B cell–activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary B cell survival and development. A role for this cytokine in antigen-driven B cell responses has been suggested but current data in this regard are limited. A BAFF receptor expressed by B cells (BAFF-R/BR3) is defective in A/WySnJ mice which exhibit a phenotype similar to BAFF-deficient (BAFF−/−) animals. Here, we show that although GC responses can be efficiently induced in both A/WySnJ and BAFF−/− mice, these responses are not sustained. In BAFF−/− mice, this response is rapidly attenuated and accompanied by perturbed follicular dendritic cell development and immune complex trapping. In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response. These data demonstrate a multifaceted role for the BAFF pathway in regulating GC progression.

scholarly journals Arhgap25 deficiency leads to decreased numbers of peripheral blood B cells and defective germinal center reactions

2020 ◽  
Author(s):  
Silke E. Lindner ◽  
Colt A. Egelston ◽  
Stephanie M. Huard ◽  
Peter P. Lee ◽  
Leo D. Wang
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Peripheral Blood ◽  
Cell Development ◽  
B Cell Development ◽  
Dependent Manner ◽  
B Cell Differentiation ◽  
Nucleotide Exchange

ABSTRACTRho family GTPases are critical for normal B cell development and function and their activity is regulated by a large and complex network of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). However, the role of GAPs in B cell development is poorly understood. Here we show that the novel Rac-GAP ARHGAP25 is important for B cell development in mice in a CXCR4-dependent manner. We show that Arhgap25 deficiency leads to a significant decrease in peripheral blood B cell numbers, as well as defects in mature B cell differentiation. Arhgap25-/- B cells respond to antigen stimulation in vitro and in vivo but have impaired germinal center formation and decreased IgG1 class switching. Additionally, Arhgap25-/- B cells exhibit increased chemotaxis to CXCL12. Taken together, these studies demonstrate an important role for Arhgap25 in peripheral B cell development and antigen response.

scholarly journals CD73 mediates adhesion of B cells to follicular dendritic cells

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1755-1764 ◽  
Author(s):  
L Airas ◽  
S Jalkanen
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Intracellular Signaling ◽  
Follicular Dendritic Cells ◽  
Adhesion Protein ◽  
Follicular Dendritic ◽  
Vascular Adhesion

Abstract Lymphocyte-vascular adhesion protein-2 was recently identified as CD73. The CD73 molecule, otherwise known as ecto-5′-nucleotidase, is a lymphocyte maturation marker that is involved in intracellular signaling, and lymphocyte proliferation and activation. We now show that CD73, in addition to mediating lymphocyte binding to endothelial cells, also mediates adhesion between B cells and follicular dendritic cells (FDC), as a monoclonal antibody (MoAb) against CD73 inhibited the aggregation of isolated germinal center B cells and FDC in vitro. Cytocentrifuge preparations of isolated germinal center cells and two- color immunofluorescence stainings of different tonsillar B-cell populations show that CD73 is expressed on FDC and on small, recirculating IgD+ B cells, but only on a few B cells inside the germinal center. Thus, we propose that CD73 on FDC has an important role in controlling B cell-FDC interactions and B-cell maturation in germinal centers.

Follicular Dendritic Cell (FDC)-Induced Microrna-Mediated up-Regulation of PRDM1 and Down-Regulation of BCL6 in Germinal Center B Lymphocytes: A Potential Mechanism for B-Cell Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4588-4588
Author(s):  
Jianhong Lin ◽  
Tint Lwin ◽  
Jianjun Zhao ◽  
Jie Zhao ◽  
Luis Crespo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Follicular Dendritic Cells ◽  
B Cell Differentiation ◽  
Follicular Dendritic

Abstract Abstract 4588 B-cell differentiation process is tightly regulated by suppression or induction of specific transcription factors. Among various transcriptional regulators, BCL6 and PRDM-1 are master regulators for germinal center (GC) formation and terminal B-cell differentiation. Dysregulation of BCL6 and PRDM-1 have been associated with lymphomagenesis. However how these transcription factors are regulated and what determines their expression are unclear. Given that follicular dendritic cells (FDC) closely interact with B cells within the GC, provide survival signal to protect B cells from apoptosis and are essential for the differentiation of GC B cells, we used an in vitro FDC-B-cell co-culture model to explore the role of FDC-B cell interaction and FDC-induced miRNA in the regulation of BCL6 and PRDM-1 expression. In this study 1) we revealed that follicular dendritic cells (FDCs, HK) regulate expression of transcription factor (BCL6, and PRDM1) via cell-cell contact, 2) we showed that FDCs regulate expression of B-cell survival and differentiation-related microRNAs, 3) we demonstrated that microRNAs regulate expression of transcription factors BCl6 and PRDM1 and 4) we documented that follicular dendritic cells regulate expression of transcription factor (BCL6, and PRDM1) through microRNAs and plays an important role in B-differentiation. These studies establish new molecular mechanisms for regulation of BCL6 and PRDM-1. FDC-induce miRNA mediated down- and up-regulation of transcriptional factors may contribute to the phenotype maintenance of GC, and pathogenesis of non-Hodgkin's lymphoma (NHL) by interfering with normal B-cell terminal differentiation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CD73 mediates adhesion of B cells to follicular dendritic cells

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1755-1764 ◽  
Author(s):  
L Airas ◽  
S Jalkanen
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Intracellular Signaling ◽  
Follicular Dendritic Cells ◽  
Adhesion Protein ◽  
Follicular Dendritic ◽  
Vascular Adhesion

Lymphocyte-vascular adhesion protein-2 was recently identified as CD73. The CD73 molecule, otherwise known as ecto-5′-nucleotidase, is a lymphocyte maturation marker that is involved in intracellular signaling, and lymphocyte proliferation and activation. We now show that CD73, in addition to mediating lymphocyte binding to endothelial cells, also mediates adhesion between B cells and follicular dendritic cells (FDC), as a monoclonal antibody (MoAb) against CD73 inhibited the aggregation of isolated germinal center B cells and FDC in vitro. Cytocentrifuge preparations of isolated germinal center cells and two- color immunofluorescence stainings of different tonsillar B-cell populations show that CD73 is expressed on FDC and on small, recirculating IgD+ B cells, but only on a few B cells inside the germinal center. Thus, we propose that CD73 on FDC has an important role in controlling B cell-FDC interactions and B-cell maturation in germinal centers.

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