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

Objective The 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. Methods We generated CD19.Cre(+/-) alpha 4-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. Results A genetic ablation of alpha 4-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(+/-) alpha 4-integrinfl/fl mice was unchanged during MOG(p35-55)-induced EAE. Adoptive transfer of purified CD19(+) B cells from CD19.Cre(+/-) alpha 4-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(+/-) alpha 4-integrin(fl/fl) mice caused worse clinical EAE than was observed in MOGp35-55-immunized C57BL/6 WT control mice that did not receive adoptively transferred CD19(+) B cells. Conclusions Observations made in CD19. Cre(+/-) alpha 4-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.