LR1, A LIPOPOLYSACCHARIDE-RESPONSIVE FACTOR WITH BINDING-SITES IN THE IMMUNOGLOBULIN SWITCH REGIONS AND HEAVY-CHAIN ENHANCER

In nuclear extracts of primary murine B lymphocytes cultured with LPS we have identified an inducible DNA-binding activity that is a candidate regulator of isotype-switch recombination. This LPS-responsive factor, which we refer to as LR1, is induced in LPS-cultured primary cells with kinetics that parallel isotype-switch recombination. LR1 binds sequences from the S-gamma-1, S-gamma-3, and S-alpha switch regions, as well as the heavy-chain enhancer, and these binding sites define a consensus that occurs in each of the murine switch regions. LR1 activity is present in pre-B and B-cell lines but absent from primary B cells that have not been cultured with mitogen and from highly differentiated B-cell lines. LR1-binding activity depends on phosphorylation and is lost following incubation of nuclear extracts with acid phosphatase. The LPS inducibility and phosphorylation dependence of LR1 activity suggest that this factor monitors kinase-dependent events in cell development and communicates them to the chromosome. The locations of its binding sites and the kinetics of its induction are consistent with a role for LR1 in regulation of isotype switching.