Regulation of lipopolysaccharide- and IL-4-induced immunoglobulin heavy chain gene activation: differential roles for CD45 and Lyb-2.

Abstract

We have demonstrated that CD45, a receptor-type protein tyrosine phosphatase, selectively regulates IgG production at the generative phase of precursors of IgG producers whereas Lyb-2 regulates IgG1 production induced by IL-4 in lipopolysaccharide (LPS)-activated B cells by acting on the generation of IgG1 precursor cells. These results point to an interesting possibility that both CD45 and Lyb-2 mediate a critical regulatory step(s) in IgG class switching. The present study was conducted to examine this possibility by elucidating the molecular mechanisms whereby CD45 and Lyb-2 control IgG synthesis in B cells activated by LPS and IL-4. Northern blot analysis showed that steady-state levels of C gamma 3, C gamma 2b and C gamma 1, but not Cmu, mRNA in LPS-activated B cells were reduced approximately 3- to 5-fold by CD45 mAb, and that the C gamma 1 mRNA level in B cells activated by LPS and IL-4 was significantly decreased by Lyb-2 mAb and CD45 mAb. Further, CD45 mAb inhibited expression of germline gamma 2b and gamma 3 transcripts induced by LPS and germline gamma 1 transcript expression induced by IL-4 plus LPS, but caused no inhibition in IL-4-induced germline gamma 1 transcript expression. In contrast, Lyb-2 mAb did not exert any inhibitory effect on the generation of germline gamma 1 transcripts induced by IL-4 and LPS or by IL-4 alone.(ABSTRACT TRUNCATED AT 250 WORDS)