The commitment of secretory cells to the selective expression of immunoglobulin CH genes is determined by the available concentrations of the triggering ligand.
The property of lipopolysaccharide to induce B cells to both proliferate and differentiate to IgM, IgG3 and IgG2b expression can be ascribed either to a precommitted sequence of molecular events in the activated B cells or, alternatively, to separate activities which independently modulate the two events. To discriminate between these two possibilities we have investigated the relationship between the doses of the polyclonal stimulus and the commitment of the activated cells to proliferate and to produce various isotypes. Low doses of ligand supported proliferation as well as IgM but not IgG2b secretion. On the contrary, high doses of the same ligand were less efficient in supporting proliferation but strongly induced heavy chain class switch. The effect of lipopolysaccharide concentrations on CH genes expression decayed with the distance from mu to the respective C gamma gene. Although we could define different B cell subsets on the basis of their proliferative response to various doses of the ligand, all these B subpopulations were found to be multipotential in terms of their switching capacity. Taken together our data show that in lipopolysaccharide cultures B cell proliferation and heavy chain switch are two events completely dissociable on the basis of their inducing requirements.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins; D008024:Ligands; D008070:Lipopolysaccharides