Activation and trafficking of peritoneal B1a B-cells in response to amphibole asbestos

Our plain-English summary of Activation and trafficking of peritoneal B1a B-cells in response to amphibole asbestos, by J.C. Pfau, K. Hurley, C. Peterson, et al (Journal of Immunotoxicology, 2014).

The study

• Authors: J.C. Pfau, K. Hurley, C. Peterson, L. Coker, C. Fowers, R. Marcum
• Journal: Journal of Immunotoxicology
• Published: 2014;11(1):90-8
• Type of article: Case report
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

B1a B-cells are concentrated in peritoneal and pleural cavities, are producers of 'natural auto-antibodies', and have been implicated in autoimmune responses. Their numbers are increased in humans and mice with systemic autoimmune diseases, but their role in the immune pathology is not known. Asbestos causes pulmonary, pleural, and peritoneal pathologies by accessing these tissues after inhalation. Amphibole asbestos has been shown to elicit immune dysfunction, including chronic inflammation, fibrosis, and autoantibody production. This study tested the hypothesis that asbestos affects immune dysfunction by activating B1a B-cells to traffic to secondary lymphatic tissue. C57Bl/6 mice were exposed to amphibole asbestos (Libby 6-Mix) either endotracheally or intraperitoneally, and the B1a B-cells in pleural or peritoneal compartments were tested by multi-parameter flow cytometry. Adoptive transfer of peritoneal lymphocytes from CD45.1 transgenic to wild-type mice was used to track the migration. The percentage and numbers of B1a B-cells in pleural and peritoneal cavities decreased 3-6 days following exposure. During that time, asbestos exposure led to a decrease in cells expressing alpha-4 (α4) integrin and MHC II antigen. Peritoneal cells treated in vitro showed decreased α4 integrin with no change in CD5, IgM, or MHC II antigen. Therefore, B1a cells (IgM(+), CD5(+), MHC II(+)) traffic from the peritoneal cavity following loss of α4 integrin expression. Following adoptive transfer into the peritoneum of asbestos-exposed mice, CD45.1(+) B1a cells were detected in the spleen and mesenteric lymph nodes after 3 days, peaking at 6 days. Interestingly, the percentage of splenic suppressor B-cells (IgM(+), CD5(+), CD11b(+), CD1d(+)) decreased following amphibole exposure, demonstrating that the B1a cells did not contribute to an increased pool of suppressive B-cells. These results show that B1a B-cells respond to asbestos exposure by trafficking to secondary lymphatic tissue where they may affect ultimate immune dysfunction.

In plain English

In this laboratory study in mice, wild-type C57BL/6 mice were given Libby amphibole asbestos ("6-Mix") into the peritoneal cavity (100 micrograms per mouse) or by endotracheal instillation (60 micrograms), with saline, wollastonite, Korean tremolite or LPS as comparison treatments in particular experiments, analysed by flow cytometry. For tracking, peritoneal lymphocytes from female CD45.1 transgenic mice were transferred into wild-type recipients, which were then exposed. Intraperitoneal 6-Mix reduced the percentage and number of peritoneal B1a B-cells, while wollastonite did not; endotracheal instillation reduced pleural B1a cells within 4 days, with recovery by 8 days. Alpha-4 integrin expression on peritoneal B1a cells fell after 3 days in vivo and by 24 hours in culture, with no significant increase in apoptosis in vitro. Peritoneal IgM rose significantly; IgA and IgG did not. Adoptively transferred CD45.1 positive B1a cells were found in the spleen and mesenteric lymph nodes of exposed hosts, and the percentage of splenic lymphocytes with suppressor B-cell markers fell, at least at 3 days. The authors concluded that asbestos exposure changes B1a B-cell populations, leading to migration to spleen and lymph nodes.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment in mice: in vivo intraperitoneal and endotracheal fibre exposures, ex vivo/in vitro peritoneal cell cultures, and adoptive transfer of CD45.1 peritoneal lymphocytes into wild-type recipients, analysed by flow cytometry (the journal header mislabels the paper "CASE REPORT")
• Who was studied: Male and female C57BL/6 mice aged 6–10 weeks, housed in specific pathogen-free conditions; wild-type mice were the exposed animals, and female CD45.1 transgenic mice served as donors of peritoneal lymphocytes for the trafficking experiments; group sizes of 3–8 mice (or wells) per treatment group
• Exposure: Libby amphibole asbestos ("6-Mix", a mixture of amphibole fibres from six contaminated Libby, Montana sites), Korean tremolite asbestos, control fibre wollastonite, and LPS; given intraperitoneally at 100 micrograms per mouse or endotracheally at 60 micrograms per mouse, and in vitro at 25 to 200 micrograms per square centimetre (the scanned text prints these as "mg")
• Main results:
  • Intraperitoneal 6-Mix reduced the percentage and number of peritoneal B1a B-cells; wollastonite-treated mice showed no change from controls, and B1b, T-cell and B2 numbers did not change significantly
  • At 24 hours no reduction in peritoneal B1a cells was seen with asbestos, whereas LPS had already caused a decrease
  • In vitro exposure of peritoneal lymphocytes (25 to 200 micrograms per square centimetre) produced no significant increase in apoptosis and no loss of B1a cell numbers
  • Endotracheal instillation of 6-Mix reduced the percentage of pleural B1a B-cells within 4 days, with complete recovery by 8 days
  • Alpha-4 integrin expression on peritoneal B1a B-cells declined significantly 3 days after asbestos in vivo but not after wollastonite; it also fell in vitro by 24 hours, and was unchanged from control at 3 days after LPS
  • Intraperitoneal 6-Mix significantly raised IgM in peritoneal fluid at 3 days, with no elevation of IgA or IgG
  • The percentage of MHC II positive peritoneal B-cells fell in vivo, but MHC II expression on the remaining B1a B-cells stayed very high: saline 98.5% (SEM 0.23), 6-Mix 94% (SEM 4.7), LPS 98.2% (SEM 2.3); in vitro there was no change in MHC II antigen expression
  • Adoptively transferred CD45.1 positive peritoneal cells were detected as B1a cells in the spleen and in mesenteric lymph nodes of 6-Mix-exposed host mice, starting at 3–4 days and peaking at 6–7 days
  • Spleens of mice given 6-Mix intraperitoneally were significantly enlarged compared with saline-exposed mice after 6 days
  • The percentage of splenic lymphocytes expressing all four suppressor B-cell markers (IgM+, CD5+, CD11b+, CD1d+) was reduced in treated mice, at least at 3 days; absolute numbers were not reported
• The authors' conclusion: The authors concluded that asbestos exposure causes physiological changes in B1a B-cell populations in both pleural and peritoneal compartments, leading to detachment and migration of these cells to spleen and lymph nodes, where they may play roles in autoantibody production, antigen presentation or modulation of immune responses
• Limitations the authors state:
  • The model used could not show what the trafficked cells actually do
  • The acute decrease in splenic suppressor B-cells does not exclude a long-term protective role for B1a B-cells
  • The reason for the rapid recovery of pleural B1a B-cells is unknown, and the destination of cells leaving the pleural cavity was not determined in this study
  • Some findings were reported only as unshown data

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Libby vermiculite mine, Montana

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Amphibole Asbestos, Pathology, Chronic Inflammation, Fibrosis, Asbestos Exposure, Peritoneal Cavity, Peritoneum, Amphibole Group.

Related studies

• Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice — A. Ferro, C.N. Zebedeo, et al. (2014)
• Comparative health effects in mice of Libby amphibole asbestos and a fibrous amphibole from Arizona — J.C. Pfau, B. Buck, et al. (2017)
• Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice — J. Gilmer, K. Serve, et al. (2016)
• Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice — M. Christofidou-Solomidou, R.A. Pietrofesa, et al. (2019)
• Differential activation of the inflammasome in THP-1 cells exposed to chrysotile asbestos and Libby "six-mix" amphiboles and subsequent activation of BEAS-2B cells — M. Li, M.E. Gunter, et al. (2012)
• Long-term exposure of mesothelial cells to SV40 and asbestos leads to malignant transformation and chemotherapy resistance — A.L. Cleaver, K. Bhamidipaty, et al. (2014)

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