Abstract |
Chronic inflammation promotes the formation of ectopic lymphoid tissue morphologically resembling secondary lymphoid tissues, though it is unclear whether this is a location where Ag-specific immune responses develop or merely a site of lymphocyte accumulation. Ectopic lymphoid tissue formation is associated with many humoral autoimmune diseases, including lupus induced by tetramethylpecadentane in mice. We examined whether an immune response to 4-hydroxy-3-nitrophenyl acetyl- keyhole limpet hemocyanin ( NP-KLH) and NP-OVA develops within ectopic lymphoid tissue ("lipogranulomas") induced by tetramethylpecadentane in C57BL/6 mice. Following primary immunization, NP-specific B cells bearing V186.2 and related heavy chains as well as lambda-light chains accumulated within ectopic lymphoid tissue. The number of anti-NP-secreting B cells in the ectopic lymphoid tissue was greatly enhanced by immunization with NP-KLH. Remarkably, the H chain sequences isolated from individual lipogranulomas from these mice were diverse before immunization, whereas individual lipogranulomas from single immunized mice had unique oligo- or monoclonal populations of presumptive NP-specific B cells. H chain CDR sequences bore numerous replacement mutations, consistent with an Ag-driven and T cell-mediated response. In mice adoptively transferred with OT-II or DO11 T cells, there was a striking accumulation of OVA-specific T cells in lipogranulomas after s.c. immunization with NP-OVA. The selective colocalization of proliferating, Ag-specific T and B lymphocytes in lipogranulomas from tetramethylpecadentane-treated mice undergoing primary immunization implicates ectopic lymphoid tissue as a site where Ag-specific humoral immune responses can develop. This has implications for understanding the strong association of humoral autoimmunity with lymphoid neogenesis, which may be associated with deficient censoring of autoreactive cells.
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Authors | Jason S Weinstein, Dina C Nacionales, Pui Y Lee, Kindra M Kelly-Scumpia, Xiao-Jie Yan, Philip O Scumpia, Dustin S Vale-Cruz, Eric Sobel, Minoru Satoh, Nicholas Chiorazzi, Westley H Reeves |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 181
Issue 5
Pg. 3259-67
(Sep 01 2008)
ISSN: 1550-6606 [Electronic] United States |
PMID | 18713997
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antigens
- Immunoglobulin Heavy Chains
- Immunoglobulin Light Chains
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Topics |
- Animals
- Antibody Formation
- Antigens
(immunology)
- Autoimmunity
- B-Lymphocytes
(immunology)
- Choristoma
(pathology)
- Female
- Immunization
- Immunoglobulin Heavy Chains
- Immunoglobulin Light Chains
- Lymphoid Tissue
(pathology)
- Mice
- T-Lymphocytes
(immunology)
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