ABSTRACT
B cells activated via CD40 in vitro form striking homotypic aggregates, especially in the presence of costimuli such as anti-IgM, whereas those stimulated by anti-IgM alone do not. Blocking aggregation with anti-LFA-1alpha also significantly inhibits CD40-stimulated B cell proliferation, suggesting that homotypic adhesion is important for B cell activation via this receptor. To investigate this we have developed a culture system where murine B cells are stimulated in semi-solid agarose, which prevents cell-cell interactions. B cells respond to various mitogenic stimuli, including anti-CD40, in an essentially normal fashion when cultured in agarose. Furthermore, anti-LFA-1 exerts similar inhibitory effects on B cell proliferation regardless of whether the cells are in liquid, or semi-solid medium. These results indicate that homotypic aggregation is not necessary for CD40-stimulated B cell proliferation and the inhibitory effects of anti-LFA-1 could, therefore, be due to the delivery of a negative signal via this integrin, rather than as a result of inhibition of B cell clustering. Furthermore, reaggregation experiments indicated that anti-IgM-stimulated B cells are attracted into anti-CD40-generated clusters, even though they do not form clusters themselves. Taken together these results indicate that clustering is a consequence of B cell activation via CD40, rather than a necessary prelude to B cell proliferation. We postulate that homotypic aggregation may involve an unknown B cell-derived chemokine.
Subject(s)
B-Lymphocytes/cytology , B-Lymphocytes/immunology , Lymphocyte Activation/immunology , Animals , Antibodies, Anti-Idiotypic/immunology , Antibodies, Anti-Idiotypic/pharmacology , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , CD40 Antigens/immunology , Cell Adhesion/immunology , Cell Aggregation/drug effects , Cell Aggregation/immunology , Cell Communication/drug effects , Cell Communication/immunology , Cell Culture Techniques/methods , Intercellular Adhesion Molecule-1/immunology , Lymphocyte Function-Associated Antigen-1/immunology , Mice , Mice, Inbred C57BL , Mitogens/pharmacology , Reproducibility of Results , SepharoseSubject(s)
Analgesics , Acetaminophen , Analgesics/adverse effects , Analgesics/therapeutic use , Anti-Inflammatory Agents , Aspirin , Dextropropoxyphene , Drug Synergism , Flufenamic Acid , Humans , Indomethacin , Mefenamic Acid , Methotrimeprazine , Orphenadrine , Oxyphenbutazone , Pentazocine , Phenacetin , Phenylbutazone , Propionates , TabletsSubject(s)
Arthritis, Reactive/complications , Heart Diseases/etiology , Spinal Diseases/etiology , Adult , Aortic Valve/pathology , Aortic Valve Insufficiency/etiology , Arthritis, Reactive/diagnostic imaging , Arthritis, Reactive/pathology , Autopsy , Bone Resorption/diagnostic imaging , Bundle-Branch Block/etiology , Calcaneus/diagnostic imaging , Diagnostic Errors , Electrocardiography , Endocarditis, Subacute Bacterial/diagnosis , Heart Block/etiology , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Metatarsus/diagnostic imaging , Radiography , Sacroiliac Joint/diagnostic imaging , Spinal Diseases/diagnostic imaging , Thoracic Vertebrae/diagnostic imagingABSTRACT
A controlled trial of carbenoxolone sodium positioned-release capsules (Duogastrone) was carried out on a randomized series of 100 unselected male Service personnel with symptoms of active duodenal ulceration and supporting radiological evidence. Fifty-seven patients completed the trial, 29 in the carbenoxolone group and 28 in the control group. The carbenoxolone group was given capsules containing 50 mg carbenoxolone four times a day for 12 weeks while the controls received a capsule identical in every respect except that it did not contain carbenoxolone. All patients were assessed at fortnightly intervals and had clinical and radiological reassessments three and six months after commencing treatment. Review at three months and at six months revealed a slight but clinically insignificant trend in favour of the carbenoxolone group. As a corollary to this controlled trial, those patients (38 in all) who did not have an early remission of symptoms were removed from the trial and placed on capsules known to contain carbenoxolone. Subsequently these patients did not show an advantage for carbenoxolone.