Distinct response in maintenance of human naive and memory B cells via IL-21 receptor and TCL1/Akt pathways.
The molecular mechanisms involving in B-cell survival/proliferation are poorly understood. Here we investigated the molecules affecting the survival of human naïve and memory B cells. Without stimulation, naïve B cells survived longer than memory B cells. Moreover, the viability of memory B cells decreased more rapidly than that of naïve B cells following with Staphylococcus aureus Cowan strain (SAC), anti-immunoglobulin (Ig), or anti-CD40 stimulation, but displayed the same levels of survival following CpG DNA stimulation. We analyzed the transcriptional differences between B-cell subsets by gene expression profiling, and identified 15 genes significantly correlated to survival/proliferation. Among them, IL-21 receptor (IL-21R) and T-cell leukemia 1 (TCL1) proto-oncogene were highly expressed in naïve B cells. IL-21 induced the proliferation of both naïve and memory B cells. Marked phosphorylation of Akt was found in naïve B cells compared with memory B cells. This study suggests that naive and memory B cells are regulated by several distinct molecules, and the IL-21R and TCL1/Akt pathways might play crucial roles in naïve B cells for their maintenance.
Nagumo
Haruo
H
Department of Infection and Host Defense, Shinshu University, Asahi, Matsumoto, Nagano, Japan. naguharu123@hotmail.com
Abe
Jun
J
Kano
Hirotsugu
H
Taki
Shinsuke
S
Yamazaki
Kazuko
K
Yamazaki
Takashi
T
Kobayashi
Norimoto
N
Koike
Kenichi
K
Sugane
Kazuo
K
Saito
Hirohisa
H
Agematsu
Kazunaga
K
D000328:Adult; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D002470:Cell Survival; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D000098546:Interleukin-21
D017931:DNA Primers; D007378:Interleukins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D053655:Receptors, Interleukin-21; C090851:TCL1A protein, human; D051057:Proto-Oncogene Proteins c-akt; D000098546:Interleukin-21