Immunology Letters, 14 (1986/1987) 313-319 Elsevier IML 00855 In vivo effects of lipopolysaccharide on lymphoid and non-lymphoid cells in the mouse spleen. Suppressive and adjuvant effects of LPS on the development of specific antibody forming cells in situ Nico van Rooijen, Nel Kors and Eric Claassen Immunocytochemistry Unit, Medical Faculty, Department of Histology, Free University, Amsterdam, The Netherlands (Received 13 October 1986) (Revision received 24 November 1986) (Accepted 24 November 1986) I. Summary Mice were immunized i.v. with 2,4,6-trinitro- phenyl (TNP)-carrier conjugates and received lipo- polysaccharide (LPS) before, simultaneously with or after these antigens, in order to study the effects of LPS on the in situ development of anti-TNP antibody forming cells in the spleen. LPS given before, simultaneously with or shortly after the thymus dependent (TD) antigen TNP- keyhole limpet haemocyanin (KLH) suppressed the development of anti-TNP antibody forming cells in the spleen, but serum IgM-anti-TNP titres were not reduced, suggesting a selective inhibiting effect of LPS on the local immune response in the spleen. Splenic responses to thymus independent (TI) anti- gens TNP-Ficoll and TNP-LPS were not reduced Key words: Lipopolysaccharide; Antibody forming cell; lm- munosuppression; Immunopotentiation Abbreviations." AP = alkaline phosphatase; BSA = bovine se- rum albumin; KLH = keyhole limpet haemocyanin; LPS = lipopolysaccharide; MZ = marginal zone; PALS = periarterio- lar lymphocyte sheath; PBS = phosphate buffered saline; TD = thymus dependent; TI-1 = thymus independent type-l; TI-2 = thymus independent type-2; TNBS = trinitrobenzene sulphonic acid; TNP = trinitrophenyl Correspondence to: N. van Rooijen, Immunocytochemistry Unit, Medical Faculty, Department of Histology, Free Universi- ty, P.O. Box 7161, 1007 MC Amsterdam, The Netherlands. when these antigens were administered one day af- ter LPS. LPS given 4 days after TNP-KLH and 1 day before killing of the animals had induced se- vere alterations in splenic histology, but we found no marked influence on numbers and distribution pattern of anti-TNP forming ceils. Results indicate that the LPS induced suppression of the immune response to TD antigens in the spleen is not caused by a direct effect of LPS on antigen reactive B- lymphocytes or on the anti-TNP antibody forming cells themselves. Possible explanations for the LPS- induced immunosuppression are discussed. 2. Introduction Lipopolysaccharide (LPS) from gram-negative microorganisms has been shown to produce a wide variety of effects on lymphoid and non-lymphoid cells of the immune system in vitro [1]. LPS can ei- ther enhance [2-4] or suppress [2, 5, 6] the im- mune response, depending on the timing of antigen and LPS administration. In general, an adjuvant effect of LPS was found when antigen and LPS were given simultaneously and via the same route, under conditions in which LPS could also function as a B cell mitogen [4]. Administration of LPS one or more days before the antigen suppressed the im- mune response. In earlier studies we investigated the effects of 0165-2478 / 87 / $ 3.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division) 313