Abstract
Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs), which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA) gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig) G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA). WEB 2170 (10-6 to 10-8 M) inhibited [3H]-thymidine incorporation by up to 35% ± 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6 to 10-8 M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA) from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs.
Highlights
Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF)
We demonstrated that GC-like B lymphocytes isolated from tonsils had a high level of PAF receptor (PAFR) messenger ribonucleic acid expression when compared to more mature mantle-zone B lymphocytes and that PAF induced tonsillar B lymphocytes to produce the cytokine interleukin-4 (IL-4).[9]
We have demonstrated that both B-lymphocyte cell lines and freshly isolated tonsillar B lymphocytes express high levels of PAFR mRNA9 and that stimulation of the PAFR leads to demonstrable intracellular signalling and increased Ig production.[8,9]
Summary
Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). We have determined that platelet-activating factor (PAF), a potent lipid mediator, can abrogate apoptosis and elevate immunoglobulin levels in Blymphoblastoid cell lines.[7,8] More recently, we demonstrated that GC-like B lymphocytes isolated from tonsils had a high level of PAF receptor (PAFR) messenger ribonucleic acid (mRNA) expression when compared to more mature mantle-zone B lymphocytes and that PAF induced tonsillar B lymphocytes to produce the cytokine interleukin-4 (IL-4).[9] following antigen receptor ligation, PAFR was irreversibly down-regulated on immortalized B lymphocytes, suggesting that the optimal time for a B lymphocyte to respond to PAF is upon entering the GC.[10] The source for PAF in the lymph node that might stimulate GC B lymphocytes is unknown. We determined that a pharmacologic antagonist of PAF, WEB 2170, could alter the ability of FDCs to stimulate proliferation and immunoglobulin secretion in B lymphocytes
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