Antigen-specific B cells present cartilage proteoglycan (aggrecan) to an autoreactive T cell hybridoma derived from a mouse with proteoglycan-induced arthritis.
Cartilage proteoglycan (aggrecan)-induced polyarthritis in BALB/c mice is characterized by chronic inflammation and destruction of joint tissues similar to that observed in human rheumatoid arthritis. The immunization of mice with fetal human proteoglycan (PG) elicits specific antibodies to the immunizing antigen of which a population cross-reacts with native mouse PG. This (auto)antibody production is immediately followed by an explosive proliferation of autoreactive T cells, suggesting that PG-specific B cells may participate in antigen presentation of PG to autoreactive T cells. We therefore isolated B cells from the spleens and lymph nodes of PG-immunized mice and examined their ability to present PG to a PG-specific T cell hybridoma. The antigen-specific T cell responses elicited by B cells from PG-immunized mice (both arthritic and clinically asymptomatic) were markedly higher than those of non-immune mice and keyhole limpet haemocyanin (KLH)-immunized mice, and these B cells could present low PG concentrations. Levels of B cell presentation corresponded with the serum levels of PG-specific antibodies, implying that these B cells were presenting the PG specifically via their surface immunoglobulin. This B cell-T cell interaction was strongly dependent on MHC class II/T cell receptor (TCR), LFA-1/intercellular adhesion molecule-1 (ICAM-1) and CD28/B7 interactions, as antibodies to Ia, ICAM-1 and B7-2 (but not to B7-1) markedly reduced presentation. These data indicate that PG-specific B cells may play an essential role in governing the development of PG-induced arthritis.
Brennan
F R
FR
Department of Biochemistry, Rush Medical University, Rush-Presbyterian-St. Luke's Medical Centre, Chicago, IL 60612, USA.
Mikecz
K
K
Buzás
E I
EI
Ragasa
D
D
Cs-Szabó
G
G
Negroiu
G
G
Glant
T T
TT
D053674:Aggrecans; D000818:Animals; D017951:Antigen Presentation; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D006825:Hybridomas; D007111:Immunity, Cellular; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000009:adverse effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
C508320:Acan protein, mouse; D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans