Pertussis toxin pretreatment alters the in vivo cell division behaviour and survival of B lymphocytes after intravenous transfer

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Abstract
Pertussis toxin (PT), produced by the causative agent of whooping cough. Bordetella pertussis, contributes to the immune dysfunction seen in infected patients. Treatment of laboratory animals with purified toxin reproduces many of the biological effects exhibited in the disease state, which include lymphocytosis, adjuvant effects for IgE secretion and delayed-type hypersensitivity reactions. In previous studies, we have demonstrated that PT pretreatment of intravenously transferred lymphocytes not only results in them being held up in the blood, but also causes a profound alteration in their positioning within the spleen. Pertussis toxin pretreated lymphocytes fail to traverse the layer of marginal zone macrophages encircling the white pulp, resulting in their exclusion from the lymphoid area of the spleen. Using a novel flow cytometric assay of cell division, the studies presented here show that a significant proportion of B, but not T. lymphocytes underwent proliferation after intravenous transfer of donor splenic lymphocytes to syngeneic recipients. This proliferation was markedly reduced by PT pretreatment of lymphocytes before transfer. In contrast, the in vitro proliferative responses of B lymphocytes to anti-IgM, LPS and antibody engagement of CD40 were unimpaired by exposure to the same levels of PT. Furthermore, the rate of in vivo decay of transferred B cells was accelerated by pretreatment with PT. Together, these data suggest PT impairs the receipt of signals which promote survival and proliferation of B cells, due to altered recirculation and positioning of lymphocytes.