α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model

ObjectiveThe goal of this study was to investigate the role of CD 19⁺ B cells within the brain and spinal cord during CNS autoimmunity in a peptide-induced, primarily T-cell-mediated experimental autoimmune encephalomyelitis (EAE) model of MS. We hypothesized that CD19⁺ B cells outside the CNS drive inflammation in EAE.MethodsWe generated CD19.Cre^+/- α4-integrin^fl/fl mice. EAE was induced by active immunization with myelin oligodendrocyte glycoprotein peptide (MOG_p35-55). Multiparameter flow cytometry was used to phenotype leukocyte subsets in primary and secondary lymphoid organs and the CNS. Serum cytokine levels and Ig levels were assessed by bead array. B-cell adoptive transfer was used to determine the compartment-specific pathogenic role of antigen-specific and non-antigen-specific B cells.ResultsA genetic ablation of α4-integrin in CD19^+/- B cells significantly reduced the number of CD19⁺ B cells in the CNS but does not affect EAE disease activity in active MOG_p35-55-induced disease. The composition of B-cell subsets in the brain, primary lymphoid organs, and secondary lymphoid organs of CD19.Cre^+/- α4-integrin^fl/fl mice was unchanged during MOG_p35-55-induced EAE. Adoptive transfer of purified CD19⁺ B cells from CD19.Cre^+/- α4-integrin^fl/fl mice or C57BL/6 wild-type (WT) control mice immunized with recombinant rMOG_1-125 or ovalbumin_323-339 into MOG_p35-55-immunized CD19.Cre^+/- α4-integrin^fl/fl mice caused worse clinical EAE than was observed in MOG_p35-55-immunized C57BL/6 WT control mice that did not receive adoptively transferred CD19⁺ B cells.ConclusionsObservations made in CD19.Cre^+/- α4-integrin^fl/fl mice in active MOG_p35-55-induced EAE suggest a compartment-specific pathogenic role of CD19⁺ B cells mostly outside of the CNS that is not necessarily antigen specific.