Antigen-specific B cells present cartilage proteoglycan (aggrecan) to an autoreactive T cell hybridoma derived from a mouse with proteoglycan-induced arthritis

Abstract

SLMMARYCartilage proteoglycan (aggrecanj-induced polyarthritis in BALB/c mice is characterized by chronic inflammation and destruction of joint tissues similar to thai observed in human rheumatoid arthritis. The immunization of mice with fetal human proteoglycan (PG) elicits specific aniibodies to the initniitii/itiy antigen of which a population cross-reacts with native mouse PG. This (auto)antibody prodtiction is initnediiitely followed by an explosive proliferation of autoreactive T cells, suggesting that PG-speciftc 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-immunizcd mice and examined their ability to present PG to a PG-specific T cell hybridoma. The antigcn-speciftc T cell responses elicited by B cells from PG-immuni;ied mice (both arthritic ;tnd clinically itsyniptomatic) were nutrkedly higher thati those of non-itnniiine tnice and keyhole limpet haemocyanin (KLH)-immimi/cd mice, and these B cells could ptesent 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 surfaee immutioglobulin. Thi.s B cell T cell interaction was strongly dependent on MHC class li T cell receptor (TCR), LFA-l/interccllu!ar adhesioti molecute-l (ICAM-1) and CD2S/B7 inletactions. as antibodies to la. lCAM-1 and B7-2 (but not lo B7-1) markedly redticed presentation. These data indicate that PG-specific B cetls may play an essential role in governing the development of PG-induced arthritis.

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4+ T helper type 1 subset differentiation

“…58 In many models of autoimmunity it is evident that B cell APC function is required for the optimal induction of autoreactive CD4 + T cell responses. [10][11][12][13][14][15][16][17] Of particular interest to this study, is the demonstration that antigenspecific transgenic B cells (incapable of antibody secretion) are required for optimal anti-aggrecan CD4 + T cell activation. 14 Additionally, mice with a B cell-restricted deficiency in the CD80/86 co-stimulatory molecules 16 show reduced susceptibility to PGIA.…”

“…[7][8][9] In the context of autoimmunity, autoantigen-specific B cells have been shown to activate autoreactive CD4 + T cells. [10][11][12][13][14][15][16][17] These findings have led to the development of…”

“…[7][8][9] In the context of autoimmunity, autoantigen-specific B cells have been shown to activate autoreactive CD4 + T cells. [10][11][12][13][14][15][16][17] These findings have led to the development of Summary Effective immune responses require antigen uptake by antigen-presenting cells (APC), followed by controlled endocytic proteolysis resulting in the generation of antigen-derived peptide fragments that associate with intracellular MHC class II molecules. The resultant peptide-MHC class II complexes then move to the APC surface where they activate CD4 + T cells.…”

Autoantigen-Specific IL-10-Transduced T Cells Suppress Chronic Arthritis by Promoting the Endogenous Regulatory IL-10 Response

“…In addition, B cells invade the inflamed synovium and are implicated in the pathogenesis of RA as producers of autoantibodies (14,15) and as efficient APCs (14,16,17). Both autoreactive T and B cell responses are required to induce severe arthritis, suggesting that both lymphocyte subsets contribute to development of arthritis (9,14).…”

B-cell involvement in the pathogenesis of RA–is there a contribution of the sympathetic nervous system?

“…Some studies have been conducted that investigated the role of Ag presentation by Bcells in experimental arthritis [2,80,81]. Using B-cell-deficient mice as well as B-cells that are not capable of secreting antibodies in a model of proteoglycan-induced arthritis it was shown that both, antigen presentation but also antibody production by B-cells were needed to fully develop disease [81].…”