{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:15:56Z","timestamp":1762078556597},"reference-count":0,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1974,2,1]]},"abstract":"This study shows that LPS is not mitogenic in cultures containing B cells, or B cells and accessory adherent cells or ME, unless T cells are present. This observation rules out models of induction of antibody synthesis in which it is assumed that the delivery of a mitogenic signal by the interaction of LPS with the membrane of the B cell is in itself sufficient for B-cell induction (19). Further, it makes unlikely the proposed extrapolation of such a model to other so-called thymus-independent antigens, e.g., PVP, levan, dextran, and SIII (19).<\/jats:p>\n The mitogenic action of LPS appears to be due to its ability to complete an inductive stimulus to B cells (13). We interpret the observed thymus dependence of the B-cell response to LPS in light of a model in which two signals are obligatory for B-cell induction (14). The first signal in the inductive pathway is delivered to the antigen-sensitive cell via a conformational change in the receptor upon interaction with antigen. The second signal is delivered via the thymus-derived cooperating system. Since LPS can induce immune responses to both immunogenic and nonimmunogenic ligands (9\u201313) we envision that one signal is delivered to the B cell via specific binding of the ligand to the B-cell antigen receptor, while a second signal is delivered as a result of T-cell cooperation via membrane-bound LPS. This has been termed abnormal induction (20). In this example LPS is the foreign membrane-bound determinant in question although histocompatibility antigens (21, 22), viral determinants, or surface bound lectins could act similarly.<\/jats:p>\n In light of the above model, one observation should be pointed out. LPS inhibits the induction of a SRBC response in normal Peyer's patch cells to which adherent cells or ME is added. This inhibition appears to be a T-cell-mediated effect because it is abolished by partial depletion of the T-cell population by antitheta treatment. Since the induction of IgM producing PFC is being measured, the T-cell-dependent LPS inhibition could act either (a) by induction of T-cell \"suppression\" (23, 24) of the normal cooperating system required for a SRBC response, or (b) by the induction of such high levels of cooperating function (13) as to be inhibitory to a SRBC IgM response.<\/jats:p>\n Our observations contrast sharply with prior reports which describe LPS as a thymus-independent antigen (2\u20134) and a B-cell mitogen (5\u20138) capable of stimulating immune responses in the absence of T-cell cooperation (2\u201312). This demonstration of the thymus dependence of LPS stimulation has been possible because Peyer's patches from congenitally athymic (nude) mice are functionally a highly purified B-cell population devoid of T cells and accessory adherent cells. In this respect, earlier studies relied on nude spleen cultures and spleen cultures from thymectomized, lethally irradiated, and bone marrow-reconstituted mice (3, 4, 6\u201313). These spleen cultures which contain B cells and accessory adherent cells are recognized to be deficient but not devoid of the thymus-derived contribution to the inductive stimulus (12, 13). It could be argued that the presence of T cells and adherent cells is in fact required for the antigen-specific effect and not for the LPS effect. However, this is unlikely since our experiments show that LPS is not directly mitogenic for B cells and does not stimulate background anti-SRBC PFC. It seems unlikely that Peyer's patch antigen-sensitive cells differ from antigen-sensitive cells in the spleen in their mechanism of induction. We have shown that Peyer's patch B cells can be specifically induced by antigen, and Peyer's patch T cells mediate cooperating and killer functions. Alternately, the possibility that Peyer's patch B cells were not stimulated by LPS as a result of prior cryptic exposure to LPS (13) in the intestinal tract was excluded since cultures containing B cells, T cells, and adherent cells or ME were stimulated to DNA synthesis by LPS.<\/jats:p>\n The reason that certain antigens appear to be thymus independent may be that their repeating polymeric nature permits inductive interactions at very low levels of thymus-derived cooperation (see reference 20 for quantitative considerations). It has been stated that the inductive properties of all thymus-independent antigens are directly related to their ability to act as B-cell mitogens (19). The observation that LPS is thymus dependent for its B-cell mitogenic activity makes us question the thymus independence of any antigen.<\/jats:p>","DOI":"10.1084\/jem.139.2.407","type":"journal-article","created":{"date-parts":[[2004,6,23]],"date-time":"2004-06-23T23:23:31Z","timestamp":1088033011000},"page":"407-413","update-policy":"http:\/\/dx.doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["FUNCTIONAL CHARACTERISTICS OF PEYER'S PATCH LYMPHOID CELLS"],"prefix":"10.1084","volume":"139","author":[{"given":"Martin F.","family":"Kagnoff","sequence":"first","affiliation":[{"name":"From the Department of Medicine, University of California at San Diego and The Salk Institute for Biological Studies, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Billings","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of California at San Diego and The Salk Institute for Biological Studies, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melvin","family":"Cohn","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of California at San Diego and The Salk Institute for Biological Studies, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1974,2,1]]},"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/139\/2\/407\/1656023\/407.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/139\/2\/407\/1656023\/407.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T21:16:55Z","timestamp":1690233415000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/139\/2\/407\/6530\/FUNCTIONAL-CHARACTERISTICS-OF-PEYER-S-PATCH"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1974,2,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1974,2,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.139.2.407","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[1974,2,1]]}}}