TY - JOUR
T1 - Production of antineutriphil cytoplasm antibodies from circulating B cells in patients with systemic vasculitis
AU - Clayton, AR
AU - Savage, Caroline
PY - 2003/4/1
Y1 - 2003/4/1
N2 - The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. In certain systemic vasculitides, autoimmunity plays an important role with autoantibodies developing towards neutrophils, which are termed antineutrophil cytoplasm antibodies (ANCA). There is a growing body of evidence that T cells may contribute to the pathogenesis of ANCA-associated vasculitides. A system was set up to determine whether B cells require T cell help to produce antibodies in a peripheral blood lymphocyte (PBL) culture system enriched for B cells and dendritic cells (DC). As a control, tetanus toxoid (TT) antibody production was detected from individuals not recently immunized with tetanus vaccine when stimulated with TT antigen. Proteinase 3 (PR3) and myeloperoxidase (MPO) antibodies were produced from B cell and DC enriched cultures prior to the addition of antigen in some ANCA-positive patients with high ANCA titres, but not from patients with low ANCA titres or controls. PBMC from individuals recently immunized with tetanus vaccine were also maximally stimulated in that addition of antibody did not enhance antibody production. We conclude that this system supports a role for T cell help in the production of TT antibodies in individuals not immunized recently with tetanus vaccine. However, in patients with ANCA-associated vasculitis and controls recently immunized with tetanus vaccine, circulating B cells are apparently spontaneously producing autoantibody, possibly reflecting a system already maximally driven in vivo , and therefore masking underlying potential T cell-B cell collaboration. Such B cells may be less responsive to regulatory stimuli in vivo.
AB - The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. In certain systemic vasculitides, autoimmunity plays an important role with autoantibodies developing towards neutrophils, which are termed antineutrophil cytoplasm antibodies (ANCA). There is a growing body of evidence that T cells may contribute to the pathogenesis of ANCA-associated vasculitides. A system was set up to determine whether B cells require T cell help to produce antibodies in a peripheral blood lymphocyte (PBL) culture system enriched for B cells and dendritic cells (DC). As a control, tetanus toxoid (TT) antibody production was detected from individuals not recently immunized with tetanus vaccine when stimulated with TT antigen. Proteinase 3 (PR3) and myeloperoxidase (MPO) antibodies were produced from B cell and DC enriched cultures prior to the addition of antigen in some ANCA-positive patients with high ANCA titres, but not from patients with low ANCA titres or controls. PBMC from individuals recently immunized with tetanus vaccine were also maximally stimulated in that addition of antibody did not enhance antibody production. We conclude that this system supports a role for T cell help in the production of TT antibodies in individuals not immunized recently with tetanus vaccine. However, in patients with ANCA-associated vasculitis and controls recently immunized with tetanus vaccine, circulating B cells are apparently spontaneously producing autoantibody, possibly reflecting a system already maximally driven in vivo , and therefore masking underlying potential T cell-B cell collaboration. Such B cells may be less responsive to regulatory stimuli in vivo.
KW - T cells
KW - systemic vasculitis
KW - ANCA
KW - B cells
UR - http://www.scopus.com/inward/record.url?scp=0037387290&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2249.2003.02111.x
DO - 10.1046/j.1365-2249.2003.02111.x
M3 - Article
C2 - 12653854
SN - 1365-2249
VL - 132
SP - 174
EP - 179
JO - Clinical & Experimental Immunology
JF - Clinical & Experimental Immunology
ER -