Protective methylation of immunoglobulin and T cell receptor (TcR) gene loci prior to induction of class switch and TcR recombination

Abstract

Methylation of the S_γ1 switch region and C_γ1 constant region gene from the immunoglobulin heavy chain locus and of the J_β2 and C_β regions from the T cell receptor β chain (TcR_β) locus is compared here in murine germ‐line cells, nonlymphoid cells and lymphocytes. In germ‐line cells and in lymphocytes prior to recombination all four regions show strong methylation, i.e. most MspI sites are methylated. After activation of lymphocytes, demethylation is observed for those regions which are activated for recombination, at specific sites 5′ of S_γ1 in B cells activated with bacterial lipopolysaccharide and interleukin 4, and for J_β2 in thymocytes. In nonlymphoid cells, where these regions cannot be used for recombination, considerable demethylation is observed for all four regions analyzed as compared to lymphocytes. The result implies an important role for methylation of recombinatorial regions. Methylation may be involved in protecting them from uninduced recombination, thus allowing regulated expression of distinct genes in lymphocyte ontogeny.