• Home
  • Search Results
  • Neutrophils contribute to excess serum BAFF levels and promote CD4+ T cell and B cell responses in lupus-prone mice.

Neutrophils contribute to excess serum BAFF levels and promote CD4+ T cell and B cell responses in lupus-prone mice.

PloS one (2014-07-11)
Christine M Coquery, Nekeithia S Wade, William M Loo, Jason M Kinchen, Kelly M Cox, Chao Jiang, Kenneth S Tung, Loren D Erickson
ABSTRACT

Despite increased frequencies of neutrophils found in autoimmune diseases such as systemic lupus erythematosus (SLE), how they contribute to disease pathogenesis and the mechanisms that affect the accumulation of neutrophils are poorly understood. The aim of this study was to identify factors in autoantibody-mediated autoimmunity that controls the accumulation of spleen resident neutrophils and to determine whether neutrophils contribute to abnormal B cell responses. Increased levels of the cytokine BAFF have been linked to loss of B cell tolerance in autoimmunity, but the cellular source responsible for excess BAFF is unknown. B cell maturation antigen (BCMA) is a receptor for BAFF and is critical for the survival of bone marrow plasma cells. Paradoxically, BCMA deficiency exacerbates the formation of autoantibody-secreting plasma cells in spleens of lupus-prone mice and the reasons for this effect are not understood. Here we analyzed the phenotype, localization and function of neutrophils in spleens of healthy mice and congenic lupus-prone mice, and compared mice sufficient or deficient in BCMA expression. Neutrophils were found to be significantly increased in frequency and activation status in spleens of lupus-prone mice when BCMA was absent. Furthermore, neutrophils localized within T cell zones and enhanced CD4(+) T cell proliferation and IFNγ production through the production of BAFF. Reduced BAFF and IFNγ serum levels, decreased frequencies of IFNγ-producing T cells, germinal center B cells, and autoantibody production after neutrophil depletion indicated the involvement of neutrophils in these autoimmune traits. Thus, we have identified a novel role for BCMA to control excess BAFF production in murine lupus through restraining the accumulation of BAFF-producing neutrophils. Our data suggests that devising therapeutic strategies to reduce neutrophils in autoimmunity may decrease BAFF levels and ameliorate disease.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Formaldehyde solution, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
Sigma-Aldrich
Formaldehyde solution, for molecular biology, 36.5-38% in H2O
Sigma-Aldrich
DAPI, for nucleic acid staining
SAFC
Formaldehyde solution, contains 10-15% methanol as stabilizer, 37 wt. % in H2O
Sigma-Aldrich
Formaldehyde solution, for molecular biology, BioReagent, ≥36.0% in H2O (T)
Sigma-Aldrich
Pristane, synthetic, ≥98% (GC)
Sigma-Aldrich
Formaldehyde solution, meets analytical specification of USP, ≥34.5 wt. %
Supelco
Formaldehyde solution, stabilized with methanol, ~37 wt. % in H2O, certified reference material
Sigma-Aldrich
Diethyl azodicarboxylate solution, 40 wt. % in toluene
Sigma-Aldrich
N,N,N′,N′-Tetramethyl-p-phenylenediamine, 99%, powder
Sigma-Aldrich
Formaldehyde solution, tested according to Ph. Eur.
SAFC
Pristane, synthetic, liquid, sterile-filtered, BioReagent
Sigma-Aldrich
β-D-Allose, rare aldohexose sugar
Sigma-Aldrich
Formaldehyde-12C solution, 20% in H2O, 99.9 atom % 12C

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.