Lymphoma models for B cell activation and tolerance. I. Conditions for the anti-mu-dependent stimulation of growth in NBL, a nude B cell lymphoma

NBL is a spontaneous B cell lymphoma that originated in NIH Swiss nude mouse, and has been maintained as an in vitro line for 4 yr in our laboratory. It is surface IgM positive and expresses several B cell markers including Fc receptors, as well as Ly-1. Although clones of NBL will grow in serum-containing medium, this cell line enters a quiescent state in serum-free culture. However, in the presence of affinity-purified or monoclonal anti-mu reagents, NBL increases its rate of proliferation as measured by thymidine incorporation or in absolute cell numbers. This stimulation is specific for mu-chain, because it does not occur with anti-beta 2 microglobulin, irrelevant nonbinding antibodies, or with monoclonal anti-B cell lineage markers. Bivalent anti-mu is required, and no consistent Fc-mediated inhibition of growth has been detected. Stimulation of NBL occurs optimally at critical cell densities (greater than 3 X 10(3)/well) in the absence of serum. Therefore, we reasoned that NBL either produced or was receptive to known B cell growth factors. Although no classic IL 1 was detected in NBL supernatants, some BCGF-I-like activity was found. Finally, in the presence of LPS, both spontaneous and anti-mu-stimulated NBL growth was inhibited, a result suggesting maturation of this lymphoma. These results suggest that NBL represents an excellent model to study the growth and differentiation of B cell subsets.