Reishi polysaccharides induce immunoglobulin production through the TLR4/TLR2-mediated induction of transcription factor Blimp-1.
The polysaccharides of Ganoderma lucidum (Reishi) possess immunomodulation activities; however, their mode of molecular action in regulating each cellular subset in the immune system is still not clear. Here, we investigate the function of the main polysaccharide fraction of Reishi (Reishi-F3) in B lymphocyte activation/differentiation. We find that Reishi-F3 causes mouse splenic B cell activation and differentiation to IgM-secreting plasma cells, and the process depends on Reishi-F3-mediated induction of Blimp-1, a master regulator capable of triggering the changes of a cascade of gene expression during plasmacytic differentiation. In human peripheral B lymphocytes, although Reishi-F3 fails to induce their activation, it is able to enhance antibody secretion, which is associated with Blimp-1 mRNA induction. The function of Reishi-F3 depends on the Toll-like receptors TLR4/TLR2 as neutralizing antibodies against TLR4/TLR2 block Reishi-F3-mediated induction of Blimp-1 mRNA and Ig secretion. We have shown that interaction of Reishi-F3 with TLR4/TLR2 followed by signaling through p38 MAPK is involved in the induction of Blimp-1 mRNA, whereas signaling through ERK, p38 MAPK, JNK, and IKK complex is involved in Reishi-F3-mediated Ig secretion. Furthermore, the differential mechanism of Reishi-F3 in mouse and human B cell activation is probably due to the presence of Blimp-1 regulatory site in human CD86 promoter. These results establish the signaling and molecular mechanisms of Reishi-F3 on promoting antibody secretion.
Lin
Kuo-I
KI
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. kuoilin@gate.sinca.edu.tw
Kao
Yeong-Yi
YY
Kuo
Hui-Kai
HK
Yang
Wen-Bin
WB
Chou
Alice
A
Lin
Hsin-Hung
HH
Yu
Alice L
AL
Wong
Chi-Huey
CH
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic; D020940:Reishi / Q000737:chemistry*; D012097:Repressor Proteins / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis*
D051940:B7-2 Antigen; D007155:Immunologic Factors; D011134:Polysaccharides; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1