Regulatory B cells in autoimmune diseases: how do they work?
B lymphocytes contribute to the pathogenesis of autoimmune disorders since B-cell depletion treatment improves such diseases. However, B cells seem ambivalent. Murine strains of nonorgan-specific as well as organ-specific autoimmune conditions present with aggravated symptoms when B cells are depleted. It is thus likely that some B cells are pathogenic while other have regulatory function. There is not only one regulatory B cell (Breg) subset, but different types of Breg cells. Regulatory function can thus be ascribed to autoreactive B cells, marginal zone B cells, transitional type 2-like B cells, or CD5(+) B cells. Regulatory activity is induced only following cell activation through a B-cell receptor, CD40, and/or TLR9. Regulatory effects are then mediated by a soluble agent, such as IL-10, and/or direct cell-to-cell contacts that involve CD40 or B7 co-stimulatory molecules. Targeted cells also vary from one disease to another. Antigen-specific autoreactive T cells, dendritic cells, macrophages, and regulatory T lymphocytes can thus be either inhibited or activated to finally modulate the autoimmune response. Taken as a whole, it appears that Breg cells participate in the control of autoimmunity within a complex cellular network that may differ for each pathology. Adapted stimulation and control of regulatory activity would thus be a prerequisite to an efficient usage of these B cells as an alternative therapy for autoimmune diseases.
Lemoine
Sébastien
S
Université Européenne de Bretagne, France.
Morva
Ahsen
A
Youinou
Pierre
P
Jamin
Christophe
C
D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D055610:Antigens, CD1d; D019013:CD40 Antigens; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D023201:CD40 Ligand