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Studies on the adjuvant action of beryllium. I. Effects on individual lymph nodes.

Beryllium was injected subcutaneously (s.c.) into sheep in the form of a suspension of insoluble Be(OH)2 in isologous lymph plasma. Even in the absence of added antigen, doses of 50-150 mg induced rapid and vigorous proliferative responses in the regional lymph nodes so that large numbers of immunoblasts appeared in the efferent lymph within 4 days. Dendritic macrophages and dead white cells, which are excluded normally from efferent lymph, also appeared in significant numbers. When horseradish peroxidase was added to the injections of Be(OH)2, specific, high-affinity antibody appeared in the immunoblasts. This did not happen when the antigen was injected on its own or in combination with conventional, alum adjuvant. By the incorporation of radioactive 7Be in the injected material, it was shown that most of the Be(OH)2 remained at the site of injection and relatively little reached the node. In spite of this the cellular composition of peripheral lymph draining directly from the sites of injection showed no significant changes, and it was concluded that a 'depot' effect was unlikely to account for the heightened immune responses. These observations on the effects of beryllium are consistent with the view that its adjuvant action results from damage to intra-nodal macrophages, and that factors released from such cells caused intense immunoblastic proliferation.