Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis.
The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance.



To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-based gene therapy including a B-cell-specific Igk promoter was used.



Presentation of the CII-peptide on B cells significantly reduced the frequency and severity of arthritis as well as the serum levels of CII -specific IgG antibodies. Further, both frequency and suppressive function of regulatory T cells were increased in tolerized mice. Adoptive transfer of regulatory T cells from tolerized mice to naïve mice ameliorated the development of CII-induced arthritis.



Our data suggest that endogenous presentation of the CII-peptide on B cells is one of the key contributors to arthritis tolerance induction and maintenance.
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.
Sofia E M
SE
Andersson
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.|Sahlgrenska University Hospital, Gothenburg, Sweden.
Tove
T
Eneljung
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.|Sahlgrenska University Hospital, Gothenburg, Sweden.
Sara
S
Tengvall
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.
Pernilla
P
Jirholt
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.
Anna
A
Stern
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.
Louise
L
Henningsson
Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden.|Southern Medical University, Guangzhou, People's Republic China.
Bibo
B
Liang
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.|Sahlgrenska University Hospital, Gothenburg, Sweden.
Katrin
K
Thorarinsdottir
Department of Chemistry, BMC, Uppsala University, Uppsala, Sweden.
Jan
J
Kihlberg
Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden.|Southern Medical University, Guangzhou, People's Republic China.
Rikard
R
Holmdahl
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden.
Inga-Lill
IL
Mårtensson
Molecular Immunology Unit, UCL Institute of Child Health, London, UK.
Kenth
K
Gustafsson
Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, SE 405 30, Gothenburg, Sweden. inger.gjertsson@rheuma.gu.se.|Sahlgrenska University Hospital, Gothenburg, Sweden. inger.gjertsson@rheuma.gu.se.
Inger
I
Gjertsson
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007108:Immune Tolerance / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes
Antigen presentation; Arthritis; B cells; B lymphocytes; Collagen; Collagen type II; Gene therapy; Tolerance