Hemokinin-1 activates the MAPK pathway and enhances B cell proliferation and antibody production.
Hemokinin 1 (HK-1) is a substance P-like tachykinin peptide predominantly expressed in non-neuronal tissues. In addition to a prominent function in lymphoid development, recent studies indicate a potential role for HK-1 in immunoregulation. The current study was focused on its action on mature B cells. Despite the negligible effect on its own, HK-1 exhibited a profound influence on B cell activation elicited by several classical signals, including LPS stimulation, BCR cross-linking, and CD40 ligation. Cells therefore showed enhanced proliferation, survival, and CD80/86 expression, and produced more IgM with a higher frequency of Ab-forming cells. Biochemical analysis revealed that HK-1 alone was sufficient to induce the activation of MAPKs and the expression of Blimp-1 and Xbp-1 in B cells. Nevertheless, costimulation with a known B cell activator resulted in much enhanced phosphorylation of MAPKs and transcriptional activation of Blimp-1 and Xbp-1. Overall, these data support that HK-1 provides an important costimulatory signal for B cell activation, possibly through synergistic activation of the MAPK pathway and induction of transcription factors critical for plasmacytic differentiation.
Wang
Wei
W
Department of Immunology, Peking University Health Science Center, Beijing, China.
Li
Qian
Q
Zhang
Jun
J
Wu
Hounan
H
Yin
Yanhui
Y
Ge
Qing
Q
Zhang
Yu
Y
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D015320:Tachykinins / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; C513258:Prdm1 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D015320:Tachykinins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; C507968:hemokinin-1; D000074462:Positive Regulatory Domain I-Binding Factor 1; D048049:Extracellular Signal-Regulated MAP Kinases