Merck
  • Home
  • Search Results
  • The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development.

The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development.

Science signaling (2015-09-04)
Wai W Lin, Zuoan Yi, Laura L Stunz, Christian J Maine, Linda A Sherman, Gail A Bishop
ABSTRACT

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an adaptor protein that inhibits signaling by CD40 and by the receptor for B cell-activating factor (BAFF) and negatively regulates homeostatic B cell survival. Loss-of-function mutations in TRAF3 are associated with human B cell malignancies, in particular multiple myeloma. The cytokine interleukin-6 (IL-6) supports the differentiation and survival of normal and neoplastic plasma cells. We found that mice with a deficiency in TRAF3 specifically in B cells (B-Traf3(-/-) mice) had about twice as many plasma cells as did their littermate controls. TRAF3-deficient B cells had enhanced responsiveness to IL-6, and genetic loss of IL-6 in B-Traf3(-/-) mice restored their plasma cell numbers to normal. TRAF3 inhibited IL-6 receptor (IL-6R)-mediated signaling by facilitating the association of PTPN22 (a nonreceptor protein tyrosine phosphatase) with the kinase Janus-activated kinase 1 (Jak1), which in turn blocked phosphorylation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Consistent with these results, the number of plasma cells in the PTPN22-deficient mice was increased compared to that in the wild-type mice. Our findings identify TRAF3 and PTPN22 as inhibitors of IL-6R signaling in B cells and reveal a previously uncharacterized role for TRAF3 in the regulation of plasma cell differentiation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nitrotetrazolium Blue chloride, powder, electrophoresis grade
Sigma-Aldrich
Nitrotetrazolium Blue chloride, ≥90.0% (HPLC)
Sigma-Aldrich
IL-6 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
Anti-Phosphotyrosine Antibody, clone 4G10®, clone 4G10®, Upstate®, from mouse
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Fcgr3
Sigma-Aldrich
Interleukin-6 human, IL-6, recombinant, expressed in HEK 293 cells, suitable for cell culture
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Calcium chloride, anhydrous, BioReagent, suitable for insect cell culture, suitable for plant cell culture, ≥96.0%
Sigma-Aldrich
Calcium chloride, meets USP testing specifications
Sigma-Aldrich
IPTG, ≥99% (TLC), ≤0.1% Dioxane
Sigma-Aldrich
Isopropyl β-D-1-thiogalactopyranoside, ≥99% (TLC)
Sigma-Aldrich
Interleukin-6 human, IL-6, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Sigma-Aldrich
Calcium chloride, AnhydroBeads, −10 mesh, ≥99.99% trace metals basis
Sigma-Aldrich
Calcium chloride, anhydrous, powder, 99.99% trace metals basis
Sigma-Aldrich
Calcium chloride, AnhydroBeads, −10 mesh, ≥99.9% trace metals basis
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
SAFC
L-Glutamine
Sigma-Aldrich
Calcium chloride solution, BioUltra, for molecular biology, ~1 M in H2O
SAFC
Isopropyl β-D-1-thiogalactopyranoside
Sigma-Aldrich
Isopropyl β-D-thiogalactopyranoside solution, ReadyMade IPTG solution for Blue-white screening
Sigma-Aldrich
Interleukin-6 human, IL-6, recombinant, expressed in E. coli, Carrier Free