Activation of glomerular basement membrane-specific B cells in the renal draining lymph node after T cell-mediated glomerular injury.
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 alpha3 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.
Robertson
Julie
J
Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, 6516 M.D. Anderson Blvd, Houston, TX 77030, USA.
Wu
Jean
J
Arends
Jon
J
Zhou
Cindy
C
McMahon
John
J
Torres
Lisa
L
Lou
Ya-Huan
YH
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D007678:Kidney Glomerulus / Q000276:immunology* / Q000293:injuries / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D023421:Models, Animal; D010446:Peptide Fragments / Q000737:chemistry; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
D010446:Peptide Fragments