LPS-nonresponsive variants of mouse B cell lymphoma, 70Z/3: isolation and characterization

We have used a genetic approach to study the differentiation of B lymphocytes. The cultured murine cell line 70Z/3 resembles pre-B cells in containing the heavy chain of the immunoglobulin IgM, mu, as an internal protein in the absence of light chain, L. However, overnight incubation with the B cell mitogen lipopolysaccharide (LPS) induces the cells to mature to a B lymphocyte-like state by the induction of L chain synthesis and the appearance of IgM on the cell surface. We have used immunoselection against surface-bound IgM to isolate LPS uninducible variants of 70Z/3. These fall into two complementation groups, LPS A and LPS B. LPS A variants predominated and were found at a frequency of 1/1200. These cells were completely unresponsive to LPS. LPS B was represented by a single variant in which a subset of cells was induced to display wild-type levels of membrane-bound IgM, and the proportion of induced cells increased with prolonged incubation with LPS. We detected no structural defects in either variant group, but LPS B may represent a defect in the decision to differentiate in response to LPS.