platelet-activating factor antagonists decrease follicular dendritic-cell stimulation of human b lymphocytesplatelet-activating因子拮抗剂减少滤泡树突状细胞刺激人b淋巴细胞.pdfVIP

Original Article Platelet-Activating Factor Antagonists Decrease Follicular Dendritic-Cell Stimulation of Human B Lymphocytes Isaac Halickman, MD; Yolande Bastien, MS; Qianli Zhuang, MD, PhD; Monty B. Mazer; Baruch Toledano, MD; Bruce D. Mazer, MD Abstract Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating fac- tor (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 media- tors. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsil- lar 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 [3 H]-thymidine incorporation, and immunoglobulin (Ig) G and IgM secretion was 6 8 3 assessed by enzyme-linked immunosorbent assay (ELISA). WEB 2170 (10 to 10 M) inhibited [ H]- 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 106 to 108 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 pr