Expression of the J chain gene during B cell differentiation is inversely correlated with DNA methylation.

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Abstract
During [mouse] B cell differentiation, transcription of the J chain gene is initiated. To determine the regulatory mechanism involved, the structure of the J chain gene in cell lines representing successive stages in B cell development were analyzed. Comparison of restriction sites showed that the J chain gene does not require a rearrangement of DNA for expression; cleavage sites present in embryonic J chain DNA were preserved through all the subsequent differentiative steps. Comparison of 5-methylcytosine contents showed that J chain gene expression correlates with a loss of methyl groups. The J chain gene was heavily methylated in cell types not expressing J chain (i.e., embryo and lymphomas representative of immature and mature B cells) and significantly less methylated in cell lines representative of antigen-stimulated lymphocytes synthesizing J chain. These changes in J chain gene methylation represent a specific differentiation-induced response. Analyses of the H chain C.mu. and C.gamma.2b genes, which are expressed at earlier and later stages than the J chain gene, showed that the C.mu. sequences were undermethylated in all cell types examined whereas the C.gamma.2b sequences were undermethylated only in cell lines expressing the IgG2b protein. The primary encounter of a B cell with antigen must therefore trigger events that effect J chain gene transcription through a mechanism involving loss of methyl groups from cytosine.