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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Establishment of an immunoglobulin m antibody-forming cell response model for characterizing immunotoxicity in primary human B cells.

Authors: Lu, Haitian; Crawford, Robert B; North, Colin M; Kaplan, Barbara L F; Kaminski, Norbert E

Published In Toxicol Sci, (2009 Dec)

Abstract: Rodent models have been extensively utilized to identify putative human immunotoxicants; however, even when immunotoxicity is established, uncertainty remains whether the effects are predictive of human risk. Therefore, the objective of this study was to establish a polyclonal immunoglobulin M (IgM) antibody-forming cell (AFC) response model to directly characterize immunotoxicity in primary mouse or human B cells. CD40 ligand (CD40L) was selected to activate B cells because it effectively drives both primary human and mouse B cells in vitro to AFC in a physiologically relevant manner to mimic T-cell-dependent antibody responses in vivo. In this model, the IgM AFC response is induced by cell surface-expressed CD40L and promoted by recombinant cytokines. Reported here are the conditions required to induce IgM AFC responses using mouse splenic B cells or human peripheral blood B cells, allowing for species comparisons. Moreover, less than one order of magnitude difference was observed in the CD40L-induced B-cell AFC responses based on data from multiple donors. In addition to antibody production, proliferation and phenotypic changes characteristic of B-cell activation as well as the plasma cell phenotype were also significantly induced. Finally, two well-characterized immunotoxicants, arsenic and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, using the CD40L-induced IgM AFC response were compared in both mouse and human B cells. Collectively, an IgM AFC response model is described that can be applied to assess the sensitivity of antibody responses to modulation by xenobiotics using mouse as well as human primary B cells.

PubMed ID: 19767444 Exiting the NIEHS site

MeSH Terms: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/toxicity; Animals; Antibody Formation*; Antigens, CD/immunology; Arsenic/toxicity; B-Lymphocytes/cytology; B-Lymphocytes/drug effects; B-Lymphocytes/immunology*; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunoglobulin M/immunology*; Immunophenotyping; Mice; Mice, Inbred C57BL

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