scholarly journals Visualizing B cell capture of cognate antigen from follicular dendritic cells

2009 ◽  
Vol 206 (7) ◽  
pp. 1485-1493 ◽  
Author(s):  
Kazuhiro Suzuki ◽  
Irina Grigorova ◽  
Tri Giang Phan ◽  
Lisa M. Kelly ◽  
Jason G. Cyster
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
B Cell ◽  
Information Transfer ◽  
Surface Proteins ◽  
Follicular Dendritic Cells ◽  
Cell Capture ◽  
Cognate Antigen ◽  
Follicular Dendritic ◽  
Antigen Presenting

The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs. B cell CXCR5 expression was required, and encounter with FDC-associated antigen could be detected for >1 wk after immunization. B cell–FDC contact times were often brief but occasionally persisted for >30 min, and B cells sometimes acquired antigen together with FDC surface proteins. These observations establish that FDCs can serve as sites of B cell antigen capture, with their prolonged display time ensuring that even rare B cells have the chance of antigen encounter, and they suggest possible information transfer from antigen-presenting cell to B cell.

scholarly journals Follicular dendritic cells help resting B cells to become effective antigen-presenting cells: induction of B7/BB1 and upregulation of major histocompatibility complex class II molecules.

1993 ◽  
Vol 178 (6) ◽  
pp. 2055-2066 ◽  
Author(s):  
M H Kosco-Vilbois ◽  
D Gray ◽  
D Scheidegger ◽  
M Julius
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
B Cells ◽  
Major Histocompatibility Complex Class ◽  
B Cell ◽  
Antigen Presenting Cells ◽  
Follicular Dendritic Cells ◽  
Complex Class ◽  
Histocompatibility Complex ◽  
Antigen Presenting

This study was designed to investigate whether follicular dendritic cells (FDC) can activate B cells to a state in which they can function as effective antigen-presenting cells (APC). High buoyant density (i.e., resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing FDC, after which their capacity to process and present to an OVA-specific T cell clone was assessed. The efficacies of alternative sources of antigen and activation signals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig receptors, induced the most potent APC function. Analysis by flow cytometry revealed that within 24 h of coculture with FDC, a significant percentage of B cells increased in size and expressed higher levels of major histocompatibility complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occurred, but only when exposed to the FDC bearing DNP. Taken together, the results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. The relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.

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 Follicular dendritic cells inhibit human B-lymphocyte proliferation

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1284-1288 ◽  
Author(s):  
AS Freedman ◽  
JM Munro ◽  
K Rhynhart ◽  
P Schow ◽  
J Daley ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Inhibitory Effect ◽  
Germinal Centers ◽  
Follicular Dendritic Cells ◽  
Neoplastic Processes ◽  
Follicular Dendritic

Abstract In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected.

scholarly journals Follicular dendritic cells inhibit human B-lymphocyte proliferation

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1284-1288 ◽  
Author(s):  
AS Freedman ◽  
JM Munro ◽  
K Rhynhart ◽  
P Schow ◽  
J Daley ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Inhibitory Effect ◽  
Germinal Centers ◽  
Follicular Dendritic Cells ◽  
Neoplastic Processes ◽  
Follicular Dendritic

In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected.

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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