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

Methylation of the S gamma 1 switch region and C gamma 1 constant region gene from the immunoglobulin heavy chain locus and of the J beta 2 and C beta regions from the T cell receptor beta chain (TcR beta) 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 Msp I sites are methylated. After activation of lymphocytes, demethylation is observed for those regions which are activated for recombination, at specific sites 5' of S gamma 1 in B cells activated with bacterial lipopolysaccharide and interleukin 4, and for J beta 2 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.