Abstract: 230
Type: Oral
While MS has traditionally been thought of as principally a T cell-mediated disease, the substantial impact of selective B cell targeting on disease activity underscores key roles for B cells at least in the relapsing biology of MS. In addition to their capacity to differentiate into antibody-secreting cells with consequent effector functions of antibody-mediated complement or cell-dependent cytotoxicity, B cells are now recognized as having important antibody-independent functions that may be relevant to MS pathogenesis. These include the potential for B cells to act as antigen presenting cells, to influence the local architecture of immune cell interactions, and to either enhance or limit local immune responses. The latter, in part, is achieved through the capacity for B cells to secrete pro-inflammatory or anti-inflammatory mediators, in a context dependent fashion. Regulation of these functions can influence disease-relevant T cell responses as well as myeloid cell responses. The contrast between the beneficial results of B cell depletion (with anti-CD20 therapies), versus the disease-exacerbating impact of atacicept (TACI-Ig) in MS patients, in spite of predictions of therapeutic benefits from animal models, call for a better understanding of the multiple roles that distinct human B cell responses likely play in the different disease compartments and throughout the clinical course of MS.
Disclosure: Dr. Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Biogen Idec, Diogenix, Roche/Genentech, Sanofi-Genzyme, GlaxoSmithKline, Medimmune, Novartis, Ono Pharma, Teva Neuroscience, Celgene/Receptos Inc, and Merck/EMD Serono.
Off label discussion of B cell directed therapies will be included to illustrate biological proof-of-principle.
Abstract: 230
Type: Oral
While MS has traditionally been thought of as principally a T cell-mediated disease, the substantial impact of selective B cell targeting on disease activity underscores key roles for B cells at least in the relapsing biology of MS. In addition to their capacity to differentiate into antibody-secreting cells with consequent effector functions of antibody-mediated complement or cell-dependent cytotoxicity, B cells are now recognized as having important antibody-independent functions that may be relevant to MS pathogenesis. These include the potential for B cells to act as antigen presenting cells, to influence the local architecture of immune cell interactions, and to either enhance or limit local immune responses. The latter, in part, is achieved through the capacity for B cells to secrete pro-inflammatory or anti-inflammatory mediators, in a context dependent fashion. Regulation of these functions can influence disease-relevant T cell responses as well as myeloid cell responses. The contrast between the beneficial results of B cell depletion (with anti-CD20 therapies), versus the disease-exacerbating impact of atacicept (TACI-Ig) in MS patients, in spite of predictions of therapeutic benefits from animal models, call for a better understanding of the multiple roles that distinct human B cell responses likely play in the different disease compartments and throughout the clinical course of MS.
Disclosure: Dr. Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Biogen Idec, Diogenix, Roche/Genentech, Sanofi-Genzyme, GlaxoSmithKline, Medimmune, Novartis, Ono Pharma, Teva Neuroscience, Celgene/Receptos Inc, and Merck/EMD Serono.
Off label discussion of B cell directed therapies will be included to illustrate biological proof-of-principle.