Contributions
Abstract: P440
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Objective: The efficacy of B cell depleting therapy in Multiple Sclerosis (MS) has renewed interest in the function of B cells in this disease. We tested the importance of B cell-derived expression of transforming growth factor (TGF)-β1, a regulatory cytokine with pleiotropic functions in control of T cell responses, in autoimmune neuroinflammation.
Background: Evidence suggests that some B cell subsets may have an important role in immune regulation of central nervous system (CNS) autoimmunity. While data indicate a role for TGF-β1 expression in regulatory B cell (Breg) functions, this mechanism has not yet been tested in autoimmune neuroinflammation.
Design and methods: Transgenic mice that cannot express TGF-β1 in B cells (B-TGF-β1-/-) were tested in experimental autoimmune encephalomyelitis (EAE) induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG), a B and T cell-mediated mouse model of MS.
Results: In this EAE model, B-TGF-β1-/- mice showed an earlier onset of neurologic impairment and markedly increased cumulative disease severity compared to their control littermates. Exacerbated EAE susceptibility in B-TGF-β1-/- mice was associated with augmented encephalitogenic autoimmune
T helper (Th)1/17 responses in the peripheral immune compartment and the CNS. Moreover, selective B cell TGF-β1-deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity.
Conclusion and Relevance: Collectively our data suggest that B cells can down-regulate function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings which may be relevant to B cell-targeted therapies.
Disclosure: K. Bjarnadóttir reports no disclosures.
M. Benkhoucha reports no disclosures.
M.S. Weber is an academic editor for PLoS One and is supported by grants from the National Multiple Sclerosis Society (NMSS; PP 1660), the DFG (WE 3547/4-1), and the ProFutura Programm of the Universitätsmedizin Göttingen.
D. Merkler reports no disclosures.
N. Payne reports no disclosures.
C.C. Bernard reports no disclosures.
N. Molnarfi reports no disclosures and received grant support for this work from the Swiss MS Society (SMSS) and from an advanced researcher exchange 2011 fellowship from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Foundation.
P.H. Lalive is on the scientific advisory board for Biogen-Idec and Novartis and received travel funding and/or speaker honoraria from Biogen-Idec, Teva, and Merck Serono. Supported by grants to P.H. Lalive from the Swiss National Science Foundation (310030-153164) and the SMSS.
Abstract: P440
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Objective: The efficacy of B cell depleting therapy in Multiple Sclerosis (MS) has renewed interest in the function of B cells in this disease. We tested the importance of B cell-derived expression of transforming growth factor (TGF)-β1, a regulatory cytokine with pleiotropic functions in control of T cell responses, in autoimmune neuroinflammation.
Background: Evidence suggests that some B cell subsets may have an important role in immune regulation of central nervous system (CNS) autoimmunity. While data indicate a role for TGF-β1 expression in regulatory B cell (Breg) functions, this mechanism has not yet been tested in autoimmune neuroinflammation.
Design and methods: Transgenic mice that cannot express TGF-β1 in B cells (B-TGF-β1-/-) were tested in experimental autoimmune encephalomyelitis (EAE) induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG), a B and T cell-mediated mouse model of MS.
Results: In this EAE model, B-TGF-β1-/- mice showed an earlier onset of neurologic impairment and markedly increased cumulative disease severity compared to their control littermates. Exacerbated EAE susceptibility in B-TGF-β1-/- mice was associated with augmented encephalitogenic autoimmune
T helper (Th)1/17 responses in the peripheral immune compartment and the CNS. Moreover, selective B cell TGF-β1-deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity.
Conclusion and Relevance: Collectively our data suggest that B cells can down-regulate function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings which may be relevant to B cell-targeted therapies.
Disclosure: K. Bjarnadóttir reports no disclosures.
M. Benkhoucha reports no disclosures.
M.S. Weber is an academic editor for PLoS One and is supported by grants from the National Multiple Sclerosis Society (NMSS; PP 1660), the DFG (WE 3547/4-1), and the ProFutura Programm of the Universitätsmedizin Göttingen.
D. Merkler reports no disclosures.
N. Payne reports no disclosures.
C.C. Bernard reports no disclosures.
N. Molnarfi reports no disclosures and received grant support for this work from the Swiss MS Society (SMSS) and from an advanced researcher exchange 2011 fellowship from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Foundation.
P.H. Lalive is on the scientific advisory board for Biogen-Idec and Novartis and received travel funding and/or speaker honoraria from Biogen-Idec, Teva, and Merck Serono. Supported by grants to P.H. Lalive from the Swiss National Science Foundation (310030-153164) and the SMSS.