B lymphocytes as autoantigen-presenting cells in the amplification of autoimmunity.
The exact role of B cells in antigen presentation to naive T cells in vivo is presently not known. Here, we demonstrate the ability of a B cell subset consisting of B7-2pos-B cells to prime autoreactive T cells in B cell-deficient mice. In contrast, B cell-deficient mice are unable to mount a similar initiation and expansion of the autoimmune response. The expression of the B7-2 costimulatory molecule as well as the specificity to a self-antigen, either murine cytochrome c or murine ribonucleoproteins (the target of autoimmunity in SLE), enabled B cells as antigen-presenting cells to induce naive lymph node T cells to proliferate and to express IFN-gamma, IL-4, IL-5, and IL-10 cytokine mRNAs. In contrast, neither adoptively transferred B7-2neg-B cells nor nonspecific B7-2pos-B cells were able to activate naive T cells. In addition, anti-B7-2 treatment prevented the in vivo expression of the IL-4, IL-5, and IFN-gamma cytokine mRNA responses. Our results suggest a major role of autoantigen-specific B7-2pos-B cells in breaking T cell tolerance to self-antigen.
Roth
R
R
Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Gee
R J
RJ
Mamula
M J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D051940:B7-2 Antigen; D003574:Cytochrome c Group / Q000276:immunology*; D005434:Flow Cytometry; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C497966:Cd86 protein, rat; D003574:Cytochrome c Group; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D017412:Ribonucleoprotein, U1 Small Nuclear