Evidence for selective transformation of autoreactive immature plasma cells in mice deficient in Fasl.

Citation data:

The Journal of experimental medicine, ISSN: 0022-1007, Vol: 200, Issue: 11, Page: 1467-78

Publication Year:
2004
Usage 23
Abstract Views 23
Captures 6
Readers 6
Citations 17
Citation Indexes 17
Repository URL:
https://mouseion.jax.org/stfb2000_2009/1019
PMID:
15583018
DOI:
10.1084/jem.20041575
PMCID:
PMC2211944
Author(s):
Zhang, Jian Qiao; Okumura, Cheryl; McCarty, Thomas; Shin, Min Sun; Mukhopadhyay, Partha; Hori, Mitsuo; Torrey, Ted A; Naghashfar, Zohreh; Zhou, Jeff X; Lee, Chang Hoon; Roopenian, Derry C; Morse, Herbert C; Davidson, Wendy F Show More Hide
Publisher(s):
Rockefeller University Press
Tags:
Medicine; Immunology and Microbiology; Antibody-Specificity; Autoimmunity; B-Lymphocytes; Cell-Transformation-Neoplastic; Gene-Expression-Profiling; Immunoglobulin-Heavy-Chains; Immunoglobulin-Variable-Region; Lymphoma-B-Cell; Membrane-Glycoproteins; Mice; Mice-Inbred-BALB-C; Mice-Inbred-C3H; Plasma-Cells
article description
Germline mutations in Fas and Fasl induce nonmalignant T cell hyperplasia and systemic autoimmunity and also greatly increase the risk of B cell neoplasms. B lymphomas occurring in Fasl mutant (gld) mice usually are immunoglobulin (Ig) isotype switched, secrete Ig, and are plasmacytoid in appearance but lack Myc translocations characteristic of other plasma cell (PC) neoplasms. Here, we explore the relationship between B cell autoreactivity and transformation and use gene expression profiling to further classify gld plasmacytoid lymphomas (PLs) and to identify genes of potential importance in transformation. We found that the majority of PLs derive from antigen-experienced autoreactive B cells producing antinuclear antibody or rheumatoid factor and exhibit the skewed Ig V gene repertoire and Ig gene rearrangement patterns associated with these specificities. Gene expression profiling revealed that both primary and transplanted PLs share a transcriptional profile that places them at an early stage in PC differentiation and distinguishes them from other B cell neoplasms. In addition, genes were identified whose altered expression might be relevant in lymphomagenesis. Our findings provide a strong case for targeted transformation of autoreactive B cells in gld mice and establish a valuable model for understanding the relationship between systemic autoimmunity and B cell neoplasia.