ANTIGEN-SPECIFIC B-CELLS PRESENT CARTILAGE PROTEOGLYCAN (AGGRECAN) TOAN 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 tis sues similar to that observed in human rheumatoid arthritis. The immun ization of mice with fetal human proteoglycan (PG) elicits specific an tibodies to the immunizing antigen of which a population cross-reacts with native mouse PG. This (auto)antibody production is immediately fo llowed by an explosive proliferation of autoreactive T cells, suggesti ng that PG-specific B cells may participate in antigen presentation of PG to autoreactive T cells. We therefore isolated B cells from the sp leens 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 arth ritic and clinically asymptomatic) were markedly higher than those of non-immune mice and keyhole limpet haemocyanin (KLH)-immunized mice, a nd these B cells could present low PG concentrations. Levels of B cell presentation corresponded with the serum levels of PG-specific antibo dies, implying that these B cells were presenting the PG specifically via their surface immunoglobulin. This B cell-T cell interaction was s trongly dependent on MHC class II/T cell receptor (TCR), LFA-1/interce llular adhesion molecule-1 (ICAM-1) and CD28/B7 interactions, as antib odies to Ia, ICAM-1 and B7-2 (but not to B7-1) markedly reduced presen tation. These data indicate that PG-specific B cells may play an essen tial role in governing the development of PG-induced arthritis.