2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2005040421v1 16/11/3256    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Robertson, J. Articles by Lou, Y.-H. Search for Related Content PubMed PubMed Citation Articles by Robertson, J. Articles by Lou, Y.-H. Related Collections Related Article

Activation of Glomerular Basement Membrane–Specific B Cells in the Renal Draining Lymph Node after T Cell–Mediated Glomerular Injury

Julie Robertson^*, Jean Wu^*, Jon Arends^*, Cindy Zhou^*, John McMahon, Lisa Torres^* and Ya-Huan Lou^*

^* Department of Diagnostic Sciences, Dental Branch; and Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, Texas

Address correspondence to: Dr. Ya-Huan Lou, Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, 6516 M.D. Anderson Blvd, Houston, TX 77030. Phone: 713-500-4059; Fax: 713-500-4416; E-mail: yahuan.lou{at}uth.tmc.edu

Received for publication April 21, 2005. Accepted for publication July 22, 2005.

Linear binding of IgG to the glomerular basement membrane (GBM) is the hallmark of anti-GBM glomerulonephritis (GN). However, the precise mechanism by which diverse autoantibodies to GBM are induced in GN has not been determined. It was demonstrated previously that a single T cell epitope pCol(28–40) derived from collagen IV 3 chain not only induced severe GN in Wistar Kyoto rats but also triggered a diversified anti-GBM antibody response through "B cell epitope spreading." In this study, an expansion of T and B cells in the renal draining lymph node (RDLN) of diseased animals after glomerular injury was observed. RDLN was demonstrated to be the location of GBM-specific B cell activation. First, B cells from RDLN of pCol(28–40)-immunized rats produced in vitro anti-GBM antibodies and antinuclear antibodies. Second, B cells specific to the peptidic B cell epitope in pCol(28–40) were absent among expanding B cells in RDLN. Those findings provided a unique opportunity to track activation of diverse GBM-specific B cells in RDLN. Expression of B lymphocyte-induced maturation protein-1, which is involved in differentiation of plasma cells, in B cells of RDLN was detected and further elevated only after T cell–mediated prominent glomerular injury (day 19). This was supported by the fact that anti-GBM antibodies became detectable only after day 20. Those results suggest that T cell–mediated glomerular injury may trigger de novo internal immunization of autoantigens released from damaged GBM, which further leads to activation of a group of GBM-specific B cells in RDLN.

Related Article

This Month’s Highlights
J. Am. Soc. Nephrol. 2005 16: 3137-3138. [Full Text] [PDF]

This article has been cited by other articles:

				P. Shah, A. Tramontano, and S. P. Makker Intramolecular Epitope Spreading in Heymann Nephritis J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3060 - 3066. [Abstract] [Full Text] [PDF]

				L. Chen, T. Hellmark, V. Pedchenko, B. G. Hudson, C. D. Pusey, J. W. Fox, and W. K. Bolton A Nephritogenic Peptide Induces Intermolecular Epitope Spreading on Collagen IV in Experimental Autoimmune Glomerulonephritis J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3076 - 3081. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673