An antisense oligonucleotide complementary to a sequence in iγ2b increases γ2b germline transcripts, stimulates B Cell DNA synthesis, and inhibits immunoglobulin secretion

Abstract

An antisense phosphorothioate (S)-oligonucleotide to a sequence in the intervening (I) region of the γ2b immunoglobulin (Ig) heavy chain gene inhibits Ig secretion by B cells stimulated with lipopolysaccharide (LPS) or LPS plus interleukin 4. It is also a striking stimulant of DNA synthesis by resting B cells. The antisense S-oligonucleotide causes a 10-20-fold increase in the expression of the γ2b germline transcript. Among mutants of the antisense S-oligonucleotide, some show all the effects whereas others are inactive. A similar hierarchy exists in the quantitative biological activities of mutant S-oligonucleotides and in their capacity to hybridize to the sense oligonucleotide, strongly suggesting that an Iγ2b sequence in the RNA transcript or in the noncoding strand of the DNA is the target of the antisense S-oligonucleotide. The possible relationship of the overexpression of the germline γ2b transcript to the biological functions of the Iγ2b antisense S-oligonucleotide is discussed.