Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression

Matsushita T., et al. 2008 J. Clin. Invest. 118, 3420-3430

Speaker: Jhen-Yu Ke (柯貞妤)                             Time:13:00~14:00, Dec. 10, 2008

Commentator: Dr. Ching-Chuan Liu (劉清泉 醫師)     Place: Room 601

Abstract:

    Experimental autoimmune encephalomyelitis (EAE), a T cell-mediated demyelinating disease of the central nervous system (CNS), is widely used as an animal model to mimic multiple sclerosis of humans. Earlier clinical studies have shown that B cells accumulate in the CNS lesions and cerebral spinal fluid of patients with multiple sclerosis, but the roles of B cells in multiple sclerosis course are unclear¹. In recent years, scientists had an argument about B cell function in EAE model. Some studies suggest that B cells may promote EAE pathogenesis, but others propose that B cells can inhibit EAE pathogenesis ^2,3. Therefore, the authors depleted B cells in mice to assess the contribution of B cells in the pathogenesis of EAE. The authors found that IL-10-producing CD1d^hiCD5⁺ regulatory B cells (B10 cells) inhibited EAE initiation, while other B cells were required for the expansion of antigen-specific T cells during disease progression. When the B cells of mice were depleted before EAE induction, the disease severity and number of CNS-infiltrating CD4⁺ T cell were increased. Using adoptive transfer of B10 cells into B cell-depleted mice, they found that B10 cells suppressed EAE initiation by secreting IL-10. However, when the B cells of mice were depleted during EAE progression, the symptoms and numbers of infiltrated T cells were reduced because of the lack of B cells that act as antigen-presenting cells to stimulate CD4⁺T cell proliferation. These results suggest the existence of two opposite actions executed by B cells during the course of EAE pathogenesis. In addition, it should be considered carefully with the disease course when using B cell depletion method to treat autoimmune diseases.

References:

1.      Williams, K.C., et al. 1994. Immunology of multiple sclerosis. Clin. Neurosci. 2, 229–245

2.      Cross, A.H., et al. 2001. B cells and antibodies in CNS demyelinating disease. J. Neuroimmunol. 112, 1–14

3.      Fillatreau, S., et al. 2002. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 3, 944–950