Dr. Alex Boyden was awarded a two-year R21 research grant entitled "Role of B Cell Interactions in CNS Autoimmune Demyelination" from the National Institute of Allergy and Infectious Diseases.

Recent success of B cell depletion therapy in US clinical trials has reinvigorated interest in determining mechanistic roles for B cells in multiple sclerosis (MS), an immune-mediated demyelinating disease of the central nervous system (CNS). The mouse model of MS (experimental autoimmune encephalomyelitis or EAE) has historically focused on active induction of demyelination through injection of a short peptide sequence within myelin oligodendrocyte glycoprotein (MOG_35-55). Other autoreactive specificities such as those directed against myelin proteolipid protein (PLP) are less-well studied. Importantly, short myelin peptides such as MOG_35-55 or PLP_178-191 do not induce B cell-dependent EAE, as the presence or absence of B cells is ancillary to disease induction and progression in mice despite B cells' clear involvement in human MS.

Study of pathogenic B cells in EAE have historically relied on a sparingly utilized B cell-dependent model involving a full length recombinant human MOG protein that is cumbersome to generate. Therefore, the state of the field calls for convenient and reliable B cell-dependent models of CNS autoimmunity. Dr. Boyden has recently developed such a model with a newly designed peptide sequence encompassing the extracellular domains of PLP (PLP_ECD), which avoids complicated recombinant protein production, shares 100% amino acid sequence homology between mouse and human, and induces a striking B cell-dependent EAE phenotype in C57BL/6J mice. The goals of the project are to fully characterize and mechanistically investigate the critical pathogenic functions of B cells in CNS autoimmune demyelination.