Molecular mechanisms for suppression of B cell differentiation

Murine B lymphocytes stimulated by bacterial lipopolysaccharide (LPS) or 8-substituted guanine nucleotides (8SGuo) proliferate and differentiate into immunoglobulin secreting plasma cells. Bivalent antibodies to the IgM receptor have opposing effects on this process. In LPS-stimulated cultures anti-mu suppresses differentiation but enhances proliferation. Both proliferation and differentiation are increased when anti-mu is added to 8SGuo-stimulated cells. In the LPS system, anti-mu treatment inhibits upregulation of transcription of a family of differentiation-related genes, including those for the mu chain, k light chain, and J chain. Induction of suppression requires synthesis of RNA and protein, suggesting involvement of a trans-acting transcriptional repressor. The possible involvement of this mechanism in B cell tolerance and cell lineage determination is discussed.