IL-7 signaling in B lymphocytes
Interleukin 7 (IL-7) is an essential cytokine for the
development and maintenance of B lymphocytes. Interleukin 7 receptor (IL-7
receptor), regulates lymphocyte survival, proliferation and
differentiation , . IL-7
receptor consists of two components, IL-7 receptor alpha chain
(IL7RA) and a common gamma chain, Interleukin 2 receptor
gamma (IL-2R gamma chain) .
IL-7 ligation to IL7RA
results in its dimerization with IL-2R gamma chain and
IL-7 receptor activation, which leads to subsequent tyrosine
phosphorylation and activation of Janus kinases 1 and 3
(JAK1 and JAK3) ,  and Src family tyrosine kinases FYN oncogene related to SRC
(Fyn) , , and v-Yes-1
Yamaguchi sarcoma viral related oncogene homolog (Lyn)
Active JAK1 and JAK3 induce
phosphorylation of Signal transducers and activators of transcription 1, 3, and 5
(STAT1, STAT3 and STAT5) and
their nuclear translocation , , .
STAT5 promotes transcription of target genes, expressing
BCL2-like 1 (Bcl-XL), Pim-1 oncogene
(Pim-1), and Cyclin D2.
Bcl-XL leads to B-cells survival.
Pim-1 and Cyclin D2 leads to
cell proliferation .
In addition, IL-7 stimulates mitogen activated protein
kinase ERK activation in B cells , , possibly, via JAK1/ Growth factor receptor-bound
protein 2 (GRB2) / Son of
sevenless homologues (SOS)/ V-raf-1 murine leukemia viral
oncogene homolog 1 (c-Raf-1)/ Harvey rat sarcoma viral
oncogene homolog (H-Ras)/ Mitogen-activated protein kinase
kinases 1 and 2 (MEK1 (MAP2K1) and MEK2
(MAP2K2) , .
IL-7-induced ERK stimulates
cell proliferation , 
Phosphorylated JAKs and Src kinases induce
Phosphoinositide-3-kinase regulatory subunit 1alpha (PI3K reg class IA
(p85-alpha)), which activates Phosphoinositide-3-kinase catalytic alpha
polypeptide (PI3K cat class IA (p 110-alpha)) that leads to
Phosphatidylinositol(3,4,5) triphosphate (PtdIns(3,4,5)P3)
conversion from PtdIns(4,5)P2.
PtdIns(3,4,5)P3 in turn induces
Akt(PKB) and 3-phosphoinositide dependent protein kinase-1
(PDK (PDPK1)) activation that promotes lymphocytes
IL-7 stimulates V(D)J recombination of Immunoglobulin H
(Igh) in B cells. V(D)J recombination is assemblage of
mature genes encoding the component chains of TCR and immunoglobulin proteins from
germ-line arrays of variable (V), diversity (D), and joining (J) gene segments during
lymphoid development . IL-7 receptor
signaling cause up regulation of the transcription factors Early B-cell factor 1
(EBF) in STAT5-, Paired box 5
(PAX5) and Transcription factor 3
(E2A)-dependent manner , , . STAT5
functions at a distinct step in distal Immunoglobulin H
(Igh) recombination in relation to
Pax5, EBF and
Oct-1 . E2A stimulate
expression of N-Myc activating B cell proliferation .
In addition, Akt(PKB) activation serves for Forkhead
boxes O1 (FKHR) negative control. It leads to inhibition of
FKHR-dependent transcription Recombination activating gene 1
and 2 (RAG1 and RAG2)
stimulating B cell differentiation. The RAG1/
RAG2 dimer recognizes the synapsis formed by the recognition motifs and
initiates the cleavage step of V(D)J recombination .
After IL-7 promotes immunoglobulin gene rearrangement,
pre-B cell receptor (pre-BCR) decreases expression of the
IL7RA and responsiveness of pre-B cells to
IL-7 signals , .
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