Regulatory B cells in autoimmune diseases: how do they work?

• Published in: Annals of the New York Academy of Sciences Vol. 1173; no. 1; pp. 260 - 267
• Main Authors: Lemoine, Sébastien, Morva, Ahsen, Youinou, Pierre, Jamin, Christophe
• Format: Journal Article
• Language: English
• Published: United States 01.09.2009
• Subjects: Animals; Antigens, CD1d - genetics; Antigens, CD1d - immunology; Antigens, CD1d - metabolism; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Autoimmune Diseases - immunology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD40 Antigens - genetics; CD40 Antigens - immunology; CD40 Antigens - metabolism; CD40 Ligand - immunology; CD40 Ligand - metabolism; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - metabolism; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-10 - metabolism; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Mice; Mice, Inbred MRL lpr; Mice, Knockout; Models, Immunological; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Signal Transduction - immunology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2009.04651.x

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.