The premise that chronic antigenic stimulation may be involved in lymphoproliferative disorders was considered in a patient with immunoblastic lymphadenopathy who had received liver extract by injection and by mouth for many years. The salient features were lymphadenopathy and hepatosplenomegaly, a predominance of lymphocytes and plasmacytoid cells with mitotic figures in lymph-node imprints, a cryoglobulin containing IgG, IgA, IgM and bound complement components, depressed serum complement levels, and Coombs-test-positive erythrocytes. Immunoglobulin concentrations per 100 ml of serum were IgG, 5900 mg, IgA, 1480 mg, and IgM, 5640 mg, with normal ranges of 710 to 1540, 60 to 490, and 37 to 204 mg, respectively. Serum precipitins to an antigen (or antigens) in the liver extract resided in the IgA and IgM classes. Complete remission followed one course of cyclophosphamide, vincristine, and prednisone. We propose that the syndrome was caused by chronic antigenic stimulation with liver extract.

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The growth and differentiation characteristics of MAC 15 murine adenocarcinoma cells, derived from routine passage in vivo for growth in vitro on a plastic substrate (MAC15j cells), were compared under conditions in which the cells were seeded onto a substrate of type-I collagen which was either attached to plastic or was released to float free in medium. Cells grown on a plastic substrate consisted of a heterogeneous, largely anaplastic population with a putative enterocytic morphology but with no evidence of junctional complexes or cell polarity typical of an epithelial phenotype. MAC 15j cells from cultures grown on a plastic substrate reestablished a moderate to well-defined degree of differentiation when transplanted back into NMRI mice. When MAC 15j cells were seeded from plastic onto type-I collagen, either attached to plastic or free-floating, tight junctional complexes were formed and the cells began to attain a more recognizable, columnar and polarised epithelial morphology. Cells grown on a type-I collagen gel which was free-floating showed a selective expression of alkaline phosphatase at the apical surfaces of approximately 10% of the cells. This expression was detectable by electron microscope histochemistry but could not be detected biochemically. Treatment of MAC 15j cells grown on a released collagen matrix with tetramethyl-urea (20mM) accelerated the expression of alkaline phosphatase activity at the apical surface as detected by microscopy.