B cell differentiation induced by lipopolysaccharide. V. Suppression of plasma cell maturation by anti-μ: mode of action and characteristics of suppressed cells

The mechanisms by which anti-μ chain antibodies suppress LPS-induced differentiation of murine B lymphocytes to plasma cells were examined as a function of age. Concentrations of anti-μ, sufficient to inhibit completely differentiation of adult B lymphocytes paradoxically enhanced cellular proliferation of LPS-stimulated cultures, whereas newborn cells, which are suppressed by much lower concentrations of anti-μ, failed to proliferate. Enhancement of proliferation of adult cultures was dependent upon both the concentration of anti-μ antibodies and the time they remained in culture. Proliferating lymphoblasts from anti-μ-treated cultures expressed H-2 and Ia alloantigens and receptors for Fc (IgG) and C3; they lacked rough endoplasmic reticulum and other ultrastructural characteristics of plasma cells and had no detectable membrane immunoglobulin. Small deposits of mouse IgM were identified in the perinuclear and Golgi regions in 95% of the cells. Cells recovered from suppressed newborn cultures lacked all of these characteristics. A population of cells, stimulated by LPS in the presence of anti-μ, appeared in the spleen between birth and 3 days, and, by 12 days of age, 35% of cells in suppressed cultures had Golgi-associated IgM. These results suggest that anti-μ inhibition of Ig synthesis in LPS-stimulated adult cells is highly specific, occurs subsequent to cross-linkage of surface IgM, and is mediated in intracellular sites by complexes of anti-μ chain antibody and IgM. Similar treatment of newborn spleen cultures results in elimination of immature B cells. These observations relate to the mechanisms of antigen-induced clonal elimination among immature B cells, as well as to the phenomenon of B cell tolerance and regulation of B cell function by anti-idiotype antibodies in adults.