Regulation of lipopolysaccharide- and IL-4-induced immunoglobulin heavy chain gene activation: differential roles for CD45 and Lyb-2.
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)
Ogimoto
M
M
Tokyo Metropolitan Institute for Neuroscience, Japan.
Mizuno
K
K
Tate
G
G
Takahashi
H
H
Katagiri
M
M
Hasegawa
K
K
Yakura
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000950:Antigens, Ly / Q000502:physiology*; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006649:Histocompatibility Antigens / Q000502:physiology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000950:Antigens, Ly; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015847:Interleukin-4; D017493:Leukocyte Common Antigens