Salmonella typhimurium mitogen induces proliferation of human B lymphocytes

The maturation of human B lymphocytes can be described as a sequence of activation, proliferation, and differentiation into immunoglobulin-secreting cells. A variety of mitogens which are T cell dependent or independent have been employed to study this process. These moieties generally induce B-cell activation and proliferation followed by differentiation, making the study of initial events difficult. This study characterizes the mitogenic activity of Salmonella typhimurium mitogen (STM), a protein fraction of S. typhimurium. Glass-nonadherent peripheral blood lymphocytes were rosetted with affinity-purified rabbit anti-human F(ab')2-coupled ox erythrocytes and separated on a Ficoll-Hypaque gradient. This population of B lymphocytes, when cultured in dilutions of STM showed dose-dependent proliferation by [3H]thymidine incorporation. Maximal proliferation occurred on Day 7 using STM at 100 micrograms/ml (control, 5692 +/- 1704 cpm; STM, 58,541 +/- 5655 cpm). On Day 7 the percentage of blast cells by Giemsa stain was 14 +/- 4% in control cultures and 52.5 +/- 8.7% with STM. ELISA quantitation of IgG and IgM in culture supernatants revealed no secretion above unstimulated controls. When B lymphocytes were enriched by a negative selection technique, significant proliferation was not observed. STM is a novel B lymphocyte mitogen which induces proliferation but not activation or differentiation of human B lymphocytes into immunoglobulin-secreting cells.