Novel suppressive function of transitional 2 B cells in experimental arthritis.
The immune system contains natural regulatory cells important in the maintenance of tolerance. Although this suppressive function is usually attributed to CD4 regulatory T cells, recent reports have revealed an immunoregulatory role for IL-10-producing B cells in the context of several autoimmune diseases including collagen-induced arthritis. In the present study, we attribute this suppressive function to a B cell subset expressing high levels of CD21, CD23, and IgM, previously identified as transitional 2-marginal zone precursor (T2-MZP) B cells. T2-MZP B cells are present in the spleens of naive mice and increase during the remission phase of arthritis. Following adoptive transfer to immunized DBA/1 mice, T2-MZP B cells significantly prevented new disease and ameliorated established disease. The suppressive effect on arthritis was paralleled by an inhibition of Ag-specific T cell activation and a reduction in cells exhibiting Th1-type functional responses. We also provide evidence that this regulatory subset mediates its suppression through the secretion of suppressive cytokines and not by cell-to-cell contact. The ability to regulate an established immune response by T2-MZP B cells endows this subset of B cells with a striking and previously unrecognized immunoregulatory potential.
Evans
Jamie G
JG
Centre for Rheumatology Research, Department of Medicine, University College London, 46 Cleveland Street, London, United Kingdom.
Chavez-Rueda
Karina A
KA
Eddaoudi
Ayad
A
Meyer-Bahlburg
Almut
A
Rawlings
David J
DJ
Ehrenstein
Michael R
MR
Mauri
Claudia
C
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D024043:Collagen Type II / Q000276:immunology; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D017464:Receptors, Complement 3d / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D024043:Collagen Type II; D007075:Immunoglobulin M; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D016753:Interleukin-10; D007371:Interferon-gamma