Transfer of immune complexes from lymphocytes to follicular dendritic cells

Stromal cells in the lymphoid organs provide a microenvironment where lymphocytes undergo various biological processes such as development, homing, clonal expansion, and differentiation. Follicular dendritic cells (FDCs) in the primary and secondary follicles of the peripheral lymphoid tissues interact with lymphocytes by contacting directly or producing diffusible molecules. To understand the biological role of human FDC at the molecular level, we developed a mAb, 3C8, that recognizes FDC but not bone marrow-derived cells. Through expression cloning and proteome analysis, we identified the protein that is recognized by 3C8 mAb, which revealed that FDC expresses prostacyclin synthase. The 3C8 protein purified from FDC-like cells indeed displayed the enzymatic activity of prostacyclin synthase and converted PGH2 into prostacyclin. In addition, prostacyclin significantly inhibited proliferation of T cells but delayed their spontaneous apoptosis. These findings may help explain why T cells constitute only a minor population compared with B cells in the germinal center.

Section: Discussionsupporting

confidence: 89%

Human Follicular Dendritic Cells Express Prostacyclin Synthase: A Novel Mechanism to Control T Cell Numbers in the Germinal Center

Lee

Kim

et al. 2005

“…Many studies have reported that Ag transport and retention on FDCs require the formation of ICs (9,(19)(20)(21). Protein Ag is not detected on FDCs in the absence of specific Abs.…”

Section: Discussionmentioning

confidence: 99%

“…They either require the formation of ICs (5, 7-9, 12, 18, 19) or the presence of larger numbers of transgenic cognate B cells (14)(15)(16)(17). In particular, retention of model protein Ags on FDCs was only observed to occur efficiently when Ag-specific Abs were present (5,7,9,(19)(20)(21). These conditions simulate the situation during a secondary immune response.…”

mentioning

confidence: 99%

Innate Immunity Mediates Follicular Transport of Particulate but Not Soluble Protein Antigen

Link¹,

Zabel²,

Schnetzler³

et al. 2012

148

128

“…Alternatively, noncognate B cells, which also can capture and transport Ag in the follicle, could potentially display Ag to GC B cells in the absence of FDC, providing a partial redundancy for the Ag-trapping role of FDC. The collapse of the GC in FDC-less mice at day 12 may reflect turnover of these particular B cells (5,41,42).…”

Section: Discussionmentioning

confidence: 99%

AID-Expressing Germinal Center B Cells Cluster Normally within Lymph Node Follicles in the Absence of FDC-M1+ CD35+ Follicular Dendritic Cells but Dissipate Prematurely

Boulianne

Ward

et al. 2013

Upon activation with T-dependent Ag, B cells enter germinal centers (GC) and upregulate activation-induced deaminase (AID). AID+ GC B cells then undergo class-switch recombination and somatic hypermutation. Follicular dendritic cells (FDC) are stromal cells that underpin GC and require constitutive signaling through the lymphotoxin (LT) β receptor to be maintained in a fully mature, differentiated state. Although it was shown that FDC can be dispensable for the generation of affinity-matured Ab, in the absence of FDC it is unclear where AID expression occurs. In a mouse model that lacks mature FDC, as well as other LT-sensitive cells, we show that clusters of AID+PNA+GL7+ Ag-specific GC B cells form within the B cell follicles of draining lymph nodes, suggesting that FDC are not strictly required for GC formation. However, later in the primary response, FDC-less GC dissipated prematurely, correlating with impaired affinity maturation. We examined whether GC dissipation was due to a lack of FDC or other LTβ receptor–dependent accessory cells and found that, in response to nonreplicating protein Ag, FDC proved to be more critical for long-term GC maintenance. Our study provides a spatial-temporal analysis of Ag-specific B cell activation and AID expression in the context of a peripheral lymph node that lacks FDC-M1+ CD35+ FDC and other LT-sensitive cell types, and reveals that FDC are not strictly required for the induction of AID within an organized GC-like environment.